4078 lines
319 KiB
Text
4078 lines
319 KiB
Text
|
|
|
|
|
|
|
|
|
|
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" lang="en-us" xml:lang="en-us" >
|
|
|
|
<head>
|
|
|
|
|
|
|
|
<!--
|
|
################################# CRAWLER WARNING #################################
|
|
|
|
- The terms of service and the robots.txt file disallows crawling of this site,
|
|
please see https://omim.org/help/agreement for more information.
|
|
|
|
- A number of data files are available for download at https://omim.org/downloads.
|
|
|
|
- We have an API which you can learn about at https://omim.org/help/api and register
|
|
for at https://omim.org/api, this provides access to the data in JSON & XML formats.
|
|
|
|
- You should feel free to contact us at https://omim.org/contact to figure out the best
|
|
approach to getting the data you need for your work.
|
|
|
|
- WE WILL AUTOMATICALLY BLOCK YOUR IP ADDRESS IF YOU CRAWL THIS SITE.
|
|
|
|
- WE WILL ALSO AUTOMATICALLY BLOCK SUB-DOMAINS AND ADDRESS RANGES IMPLICATED IN
|
|
DISTRIBUTED CRAWLS OF THIS SITE.
|
|
|
|
################################# CRAWLER WARNING #################################
|
|
-->
|
|
|
|
|
|
|
|
<meta http-equiv="content-type" content="text/html; charset=utf-8" />
|
|
<meta http-equiv="cache-control" content="no-cache" />
|
|
<meta http-equiv="pragma" content="no-cache" />
|
|
<meta name="robots" content="index, follow" />
|
|
|
|
|
|
<meta name="viewport" content="width=device-width, initial-scale=1" />
|
|
<meta http-equiv="X-UA-Compatible" content="IE=edge" />
|
|
|
|
|
|
<meta name="title" content="Online Mendelian Inheritance in Man (OMIM)" />
|
|
<meta name="description" content="Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative
|
|
compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text,
|
|
referenced overviews in OMIM contain information on all known mendelian disorders and over 15,000 genes.
|
|
OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries
|
|
contain copious links to other genetics resources." />
|
|
<meta name="keywords" content="Mendelian Inheritance in Man, OMIM, Mendelian diseases, Mendelian disorders, genetic diseases,
|
|
genetic disorders, genetic disorders in humans, genetic phenotypes, phenotype and genotype, disease models, alleles,
|
|
genes, dna, genetics, dna testing, gene testing, clinical synopsis, medical genetics" />
|
|
<meta name="theme-color" content="#333333" />
|
|
<link rel="icon" href="/static/omim/favicon.png" />
|
|
<link rel="apple-touch-icon" href="/static/omim/favicon.png" />
|
|
<link rel="manifest" href="/static/omim/manifest.json" />
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script id='mimBrowserCapability'>
|
|
function _0x5069(){const _0x4b1387=['91sZIeLc','mimBrowserCapability','15627zshTnf','710004yxXedd','34LxqNYj','match','disconnect','1755955rnzTod','observe','1206216ZRfBWB','575728fqgsYy','webdriver','documentElement','close','open','3086704utbakv','7984143PpiTpt'];_0x5069=function(){return _0x4b1387;};return _0x5069();}function _0xe429(_0x472ead,_0x43eb70){const _0x506916=_0x5069();return _0xe429=function(_0xe42949,_0x1aaefc){_0xe42949=_0xe42949-0x1a9;let _0xe6add8=_0x506916[_0xe42949];return _0xe6add8;},_0xe429(_0x472ead,_0x43eb70);}(function(_0x337daa,_0x401915){const _0x293f03=_0xe429,_0x5811dd=_0x337daa();while(!![]){try{const _0x3dc3a3=parseInt(_0x293f03(0x1b4))/0x1*(-parseInt(_0x293f03(0x1b6))/0x2)+parseInt(_0x293f03(0x1b5))/0x3+parseInt(_0x293f03(0x1b0))/0x4+-parseInt(_0x293f03(0x1b9))/0x5+parseInt(_0x293f03(0x1aa))/0x6+-parseInt(_0x293f03(0x1b2))/0x7*(parseInt(_0x293f03(0x1ab))/0x8)+parseInt(_0x293f03(0x1b1))/0x9;if(_0x3dc3a3===_0x401915)break;else _0x5811dd['push'](_0x5811dd['shift']());}catch(_0x4dd27b){_0x5811dd['push'](_0x5811dd['shift']());}}}(_0x5069,0x84d63),(function(){const _0x9e4c5f=_0xe429,_0x363a26=new MutationObserver(function(){const _0x458b09=_0xe429;if(document!==null){let _0x2f0621=![];navigator[_0x458b09(0x1ac)]!==![]&&(_0x2f0621=!![]);for(const _0x427dda in window){_0x427dda[_0x458b09(0x1b7)](/cdc_[a-z0-9]/ig)&&(_0x2f0621=!![]);}_0x2f0621===!![]?document[_0x458b09(0x1af)]()[_0x458b09(0x1ae)]():(_0x363a26[_0x458b09(0x1b8)](),document['getElementById'](_0x458b09(0x1b3))['remove']());}});_0x363a26[_0x9e4c5f(0x1a9)](document[_0x9e4c5f(0x1ad)],{'childList':!![]});}()));
|
|
</script>
|
|
|
|
|
|
|
|
<link rel='preconnect' href='https://cdn.jsdelivr.net' />
|
|
<link rel='preconnect' href='https://cdnjs.cloudflare.com' />
|
|
|
|
<link rel="preconnect" href="https://www.googletagmanager.com" />
|
|
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery@3.7.1/dist/jquery.min.js" integrity="sha256-/JqT3SQfawRcv/BIHPThkBvs0OEvtFFmqPF/lYI/Cxo=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-migrate@3.5.2/dist/jquery-migrate.js" integrity="sha256-ThFcNr/v1xKVt5cmolJIauUHvtXFOwwqiTP7IbgP8EU=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/js/bootstrap.min.js" integrity="sha256-nuL8/2cJ5NDSSwnKD8VqreErSWHtnEP9E7AySL+1ev4=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap.min.css" integrity="sha256-bZLfwXAP04zRMK2BjiO8iu9pf4FbLqX6zitd+tIvLhE=" crossorigin="anonymous">
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap-theme.min.css" integrity="sha256-8uHMIn1ru0GS5KO+zf7Zccf8Uw12IA5DrdEcmMuWLFM=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/moment@2.29.4/min/moment.min.js" integrity="sha256-80OqMZoXo/w3LuatWvSCub9qKYyyJlK0qnUCYEghBx8=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/js/bootstrap-datetimepicker.min.js" integrity="sha256-dYxUtecag9x4IaB2vUNM34sEso6rWTgEche5J6ahwEQ=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/css/bootstrap-datetimepicker.min.css" integrity="sha256-9FNpuXEYWYfrusiXLO73oIURKAOVzqzkn69cVqgKMRY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.js" integrity="sha256-a+PRq3NbyK3G08Boio9X6+yFiHpTSIrbE7uzZvqmDac=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.css" integrity="sha256-JvdVmxv7Q0LsN1EJo2zc1rACwzatOzkyx11YI4aP9PY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/devbridge-autocomplete@1.4.11/dist/jquery.autocomplete.min.js" integrity="sha256-BNpu3uLkB3SwY3a2H3Ue7WU69QFdSRlJVBrDTnVKjiA=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-validation@1.21.0/dist/jquery.validate.min.js" integrity="sha256-umbTaFxP31Fv6O1itpLS/3+v5fOAWDLOUzlmvOGaKV4=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/js-cookie@3.0.5/dist/js.cookie.min.js" integrity="sha256-WCzAhd2P6gRJF9Hv3oOOd+hFJi/QJbv+Azn4CGB8gfY=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdnjs.cloudflare.com/ajax/libs/ScrollToFixed/1.0.8/jquery-scrolltofixed-min.js" integrity="sha512-ohXbv1eFvjIHMXG/jY057oHdBZ/jhthP1U3jES/nYyFdc9g6xBpjDjKIacGoPG6hY//xVQeqpWx8tNjexXWdqA==" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script async src="https://www.googletagmanager.com/gtag/js?id=G-HMPSQC23JJ"></script>
|
|
<script>
|
|
window.dataLayer = window.dataLayer || [];
|
|
function gtag(){window.dataLayer.push(arguments);}
|
|
gtag("js", new Date());
|
|
gtag("config", "G-HMPSQC23JJ");
|
|
</script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script src="/static/omim/js/site.js?version=Zmk5Y1" integrity="sha256-fi9cXywxCO5p0mU1OSWcMp0DTQB4s8ncFR8j+IO840s="></script>
|
|
|
|
|
|
<link rel="stylesheet" href="/static/omim/css/site.css?version=VGE4MF" integrity="sha256-Ta80Qpm3w1S8kmnN0ornbsZxdfA32R42R4ncsbos0YU=" />
|
|
|
|
|
|
<script src="/static/omim/js/entry/entry.js?version=anMvRU" integrity="sha256-js/EBOBZzGDctUqr1VhnNPzEiA7w3HM5JbFmOj2CW84="></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimBootstrapDeviceSize">
|
|
<div class="visible-xs" data-mim-bootstrap-device-size="xs"></div>
|
|
<div class="visible-sm" data-mim-bootstrap-device-size="sm"></div>
|
|
<div class="visible-md" data-mim-bootstrap-device-size="md"></div>
|
|
<div class="visible-lg" data-mim-bootstrap-device-size="lg"></div>
|
|
</div>
|
|
|
|
|
|
|
|
<title>
|
|
|
|
Entry
|
|
|
|
- #262600 - PITUITARY HORMONE DEFICIENCY, COMBINED, 2; CPHD2
|
|
|
|
|
|
- OMIM
|
|
|
|
</title>
|
|
|
|
|
|
|
|
</head>
|
|
|
|
<body>
|
|
<div id="mimBody">
|
|
|
|
|
|
|
|
<div id="mimHeader" class="hidden-print">
|
|
|
|
|
|
|
|
<nav class="navbar navbar-inverse navbar-fixed-top mim-navbar-background">
|
|
<div class="container-fluid">
|
|
|
|
<!-- Brand and toggle get grouped for better mobile display -->
|
|
<div class="navbar-header">
|
|
<button type="button" class="navbar-toggle collapsed" data-toggle="collapse" data-target="#mimNavbarCollapse" aria-expanded="false">
|
|
<span class="sr-only"> Toggle navigation </span>
|
|
<span class="icon-bar"></span>
|
|
<span class="icon-bar"></span>
|
|
<span class="icon-bar"></span>
|
|
</button>
|
|
<a class="navbar-brand" href="/"><img alt="OMIM" src="/static/omim/icons/OMIM_davinciman.001.png" height="30" width="30"></a>
|
|
</div>
|
|
|
|
<div id="mimNavbarCollapse" class="collapse navbar-collapse">
|
|
|
|
<ul class="nav navbar-nav">
|
|
|
|
|
|
<li>
|
|
<a href="/help/about"><span class="mim-navbar-menu-font"> About </span></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimStatisticsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Statistics <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="statisticsDropdown">
|
|
<li>
|
|
<a href="/statistics/update"> Update List </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/entry"> Entry Statistics </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/geneMap"> Phenotype-Gene Statistics </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/paceGraph"> Pace of Gene Discovery Graph </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimDownloadsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Downloads <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="downloadsDropdown">
|
|
|
|
<li>
|
|
<a href="/downloads/"> Register for Downloads </a>
|
|
</li>
|
|
<li>
|
|
<a href="/api"> Register for API Access </a>
|
|
</li>
|
|
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li>
|
|
<a href="/contact?mimNumber=262600"><span class="mim-navbar-menu-font"> Contact Us </span></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li>
|
|
|
|
<a href="/mimmatch/">
|
|
|
|
<span class="mim-navbar-menu-font">
|
|
<span class="mim-tip-bottom" qtip_title="<strong>MIMmatch</strong>" qtip_text="MIMmatch is a way to follow OMIM entries that interest you and to find other researchers who may share interest in the same entries. <br /><br />A bonus to all MIMmatch users is the option to sign up for updates on new gene-phenotype relationships.">
|
|
MIMmatch
|
|
</span>
|
|
</span>
|
|
</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimDonateDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Donate <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="donateDropdown">
|
|
<li>
|
|
<a href="https://secure.jhu.edu/form/OMIM" target="_blank" onclick="gtag('event', 'mim_donation', {'destination': 'secure.jhu.edu'})"> Donate! </a>
|
|
</li>
|
|
<li>
|
|
<a href="/donors"> Donors </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimHelpDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Help <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="helpDropdown">
|
|
<li>
|
|
<a href="/help/faq"> Frequently Asked Questions (FAQs) </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/search"> Search Help </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/linking"> Linking Help </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/api"> API Help </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/external"> External Links </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/agreement"> Use Agreement </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/copyright"> Copyright </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li>
|
|
<a href="#" id="mimShowTips" class="mim-tip-hint" title="Click to reveal all tips on the page. You can also hover over individual elements to reveal the tip."><span class="mim-navbar-menu-font"><span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span></span></a>
|
|
</li>
|
|
|
|
|
|
</ul>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimSearch" class="hidden-print">
|
|
|
|
<div class="container">
|
|
|
|
<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
|
|
|
|
<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
|
|
<input type="hidden" id="mimSearchStart" name="start" value="1" />
|
|
<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
|
|
<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
|
|
|
|
|
|
<div class="row">
|
|
|
|
<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
|
|
<div class="form-group">
|
|
<div class="input-group">
|
|
<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
|
|
<div class="input-group-btn">
|
|
<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
|
|
<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
|
|
<ul class="dropdown-menu dropdown-menu-right">
|
|
<li class="dropdown-header">
|
|
Advanced Search
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/entry"> OMIM </a>
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/geneMap"> Gene Map </a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/history"> Search History </a>
|
|
</li>
|
|
|
|
|
|
</ul>
|
|
</div>
|
|
</div>
|
|
<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="col-lg-4 col-md-4 col-sm-4 col-xs-4">
|
|
<span class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</form>
|
|
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
<!-- <div id="mimSearch"> -->
|
|
|
|
|
|
|
|
|
|
<div id="mimContent">
|
|
|
|
|
|
|
|
<div class="container hidden-print">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
|
|
<div id="mimAlertBanner">
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
|
|
|
|
<div id="mimFloatingTocMenu" class="small" role="navigation">
|
|
|
|
<p>
|
|
<span class="h4">#262600</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="/clinicalSynopsis/262600"><strong>Clinical Synopsis</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
|
|
<a href="/phenotypicSeries/PS613038"> <strong>Phenotypic Series</strong> </a>
|
|
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#clinicalFeatures">Clinical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#inheritance">Inheritance</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#pathogenesis">Pathogenesis</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#clinicalManagement">Clinical Management</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#seeAlso"><strong>See Also</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://clinicaltrials.gov/search?cond=PITUITARY HORMONE DEFICIENCY, COMBINED" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>EuroGentest</div>
|
|
<div id="mimEuroGentestFold" class="collapse">
|
|
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=12081&Typ=Pat" title="Non-acquired panhypopituitarism" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Non-acquired panhypopituit… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=12618&Typ=Pat" title="Combined pituitary hormone deficiencies, genetic forms" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Combined pituitary hormone… </a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1347/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.diseaseinfosearch.org/x/5780" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=262600[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Orphanet</div>
|
|
<div id="mimOrphanetFold" class="collapse">
|
|
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=90695" title="Non-acquired panhypopituitarism" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Non-acquired panhypopituit…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=95494" title="Combined pituitary hormone deficiencies, genetic forms" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Combined pituitary hormone…</a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Animal Models</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://wormbase.org/resources/disease/DOID:0061020" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cell Lines</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:262600" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
|
|
|
|
<strong>SNOMEDCT:</strong> 32390006<br />
|
|
|
|
|
|
<strong>ICD10CM:</strong> E23.0<br />
|
|
|
|
|
|
<strong>ICD9CM:</strong> 253.2<br />
|
|
|
|
|
|
<strong>ORPHA:</strong> 90695, 95494<br />
|
|
|
|
|
|
<strong>DO:</strong> 0061020<br />
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
|
|
<span class="text-danger"><strong>#</strong></span>
|
|
262600
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
PITUITARY HORMONE DEFICIENCY, COMBINED, 2; CPHD2
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
PANHYPOPITUITARISM<br />
|
|
ATELIOTIC DWARFISM WITH HYPOGONADISM<br />
|
|
PITUITARY DWARFISM III<br />
|
|
HANHART DWARFISM
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/5/818?start=-3&limit=10&highlight=818">
|
|
5q35.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Pituitary hormone deficiency, combined, 2
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/262600"> 262600 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
PROP1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601538"> 601538 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/262600" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
|
|
<a href="/phenotypicSeries/PS613038" class="btn btn-info" role="button"> Phenotypic Series </a>
|
|
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/262600" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/262600" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> GROWTH </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Height </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Normal birth length <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853173&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853173</a>]</span><br /> -
|
|
Decreasing height velocity (childhood) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5393167&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5393167</a>]</span><br /> -
|
|
Proportionate short stature (if untreated) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5393168&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5393168</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/772085001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">772085001</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003508</a>]</span><br /> -
|
|
Adult height 109-137 cm <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5393169&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5393169</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Weight </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Normal birth weight <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/276712009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">276712009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0456136&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0456136</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Other </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Severe growth retardation (childhood) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5393170&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5393170</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/59576002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">59576002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/444896005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">444896005</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001510</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Face </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Frontal bossing <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/90145001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">90145001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221354&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221354</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002007</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Frontal_Bossing-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Blue sclerae <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/204164000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">204164000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q13.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q13.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0542514&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0542514</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000592" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000592</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000592" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000592</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKELETAL </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Delayed bone age <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/123983008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">123983008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0541764&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0541764</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002750" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002750</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002750" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002750</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Limbs </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Limited elbow extensibility <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4746891&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4746891</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKIN, NAILS, & HAIR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Skin </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Wrinkled skin <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/247434009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">247434009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0037301&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0037301</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100678" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100678</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100678" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100678</a>]</span><br /> -
|
|
Dry skin <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/52475004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">52475004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E50.8" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E50.8</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0043345&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0043345</a>, <a href="https://bioportal.bioontology.org/search?q=C0720057&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0720057</a>, <a href="https://bioportal.bioontology.org/search?q=C0151908&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151908</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000958" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000958</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000958" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000958</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Hypoplastic pituitary gland <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2748860&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2748860</a>]</span><br /> -
|
|
Enlarged pituitary gland <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237718009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237718009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0342422&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0342422</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012505" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012505</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012505" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012505</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> VOICE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- High-pitched voice <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/51406002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">51406002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0241703&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0241703</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001620" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001620</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001620" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001620</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ENDOCRINE FEATURES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Combined pituitary hormone deficiency <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32390006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32390006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E23.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E23.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/253.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">253.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0242343&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0242343</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000871" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000871</a>]</span><br /> -
|
|
Hypothyroidism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/40930008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">40930008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E03.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E03.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/244.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">244.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020676&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020676</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000821" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000821</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000821" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000821</a>]</span><br /> -
|
|
Hypogonadotropic hypogonadism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22053006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22053006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/33927004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">33927004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405769009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405769009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E23.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E23.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q98.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q98.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q98.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q98.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/758.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">758.7</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0271623&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0271623</a>, <a href="https://bioportal.bioontology.org/search?q=C0022735&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022735</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000044" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000044</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000044" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000044</a>]</span><br /> -
|
|
Delayed puberty <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/400003000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">400003000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/123526007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">123526007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E30.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E30.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0034012&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0034012</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000823" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000823</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000823" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000823</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Growth hormone (GH) deficiency <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5393171&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5393171</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397827003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397827003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/2109003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">2109003</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0034323" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0034323</a>]</span><br /> -
|
|
IGF-1 deficiency <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/724385009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">724385009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837475&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837475</a>]</span><br /> -
|
|
Thyroid stimulation hormone (TSH) deficiency <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5393173&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5393173</a>]</span><br /> -
|
|
Prolactin hormone (PRL) deficiency <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5393174&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5393174</a>]</span><br /> -
|
|
Luteinizing hormone (LH) deficiency <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/190481008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">190481008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0342387&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0342387</a>]</span><br /> -
|
|
Follicle stimulation hormone (FSH) deficiency <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5393175&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5393175</a>]</span><br /> -
|
|
Normal adrenocorticotropic hormone (ACTH) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5393176&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5393176</a>]</span><br /> -
|
|
Hypercholesterolemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/13644009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">13644009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1522133&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1522133</a>, <a href="https://bioportal.bioontology.org/search?q=C0020443&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020443</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003124" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003124</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003124" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003124</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Age at diagnosis, 9 months to 8 years<br /> -
|
|
Initial presentation is growth retardation caused by either GH or TSH deficiency<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by mutation in PROP paired-like homeobox 1 gene (PROP1, 601538.0001)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Pituitary hormone deficiency, combined
|
|
- <a href="/phenotypicSeries/PS613038">PS613038</a>
|
|
- 10 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
|
|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
|
<thead>
|
|
<tr>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Location</strong>
|
|
</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
|
<strong>Phenotype</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Inheritance</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />mapping key</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/848?start=-3&limit=10&highlight=848"> 1p21.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618160"> Pituitary hormone deficiency, combined or isolated, 7 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618160"> 618160 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618016"> RNPC3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618016"> 618016 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/1469?start=-3&limit=10&highlight=1469"> 1q25.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/262700"> Pituitary hormone deficiency, combined, 4 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/262700"> 262700 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602146"> LHX4 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602146"> 602146 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/3/411?start=-3&limit=10&highlight=411"> 3p14.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/182230"> Pituitary hormone deficiency, combined, 5 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/182230"> 182230 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601802"> HESX1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601802"> 601802 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/3/411?start=-3&limit=10&highlight=411"> 3p14.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/182230"> Growth hormone deficiency with pituitary anomalies </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/182230"> 182230 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601802"> HESX1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601802"> 601802 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/3/411?start=-3&limit=10&highlight=411"> 3p14.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/182230"> Septooptic dysplasia </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/182230"> 182230 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601802"> HESX1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601802"> 601802 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/3/471?start=-3&limit=10&highlight=471"> 3p12.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/620303"> Pituitary hormone deficiency, combined or isolated, 8 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/620303"> 620303 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602430"> ROBO1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602430"> 602430 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/3/476?start=-3&limit=10&highlight=476"> 3p11.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613038"> Pituitary hormone deficiency, combined or isolated, 1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613038"> 613038 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/173110"> POU1F1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/173110"> 173110 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/5/818?start=-3&limit=10&highlight=818"> 5q35.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/262600"> Pituitary hormone deficiency, combined, 2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/262600"> 262600 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601538"> PROP1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601538"> 601538 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/9/646?start=-3&limit=10&highlight=646"> 9q34.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/221750"> Pituitary hormone deficiency, combined, 3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/221750"> 221750 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600577"> LHX3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600577"> 600577 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/14/266?start=-3&limit=10&highlight=266"> 14q22.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613986"> Pituitary hormone deficiency, combined, 6 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613986"> 613986 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600037"> OTX2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600037"> 600037 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="text-right small">
|
|
<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimTextFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because combined pituitary hormone deficiency-2 (CPHD2) is caused by homozygous or compound heterozygous mutation in the PROP1 gene (<a href="/entry/601538">601538</a>) on chromosome 5q35.</p><p>For discussion of phenotypic and genetic heterogeneity of combined pituitary hormone deficiency, see CPHD1 (<a href="/entry/613038">613038</a>).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="clinicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Panhypopituitary dwarfism is not excessively rare, there probably being 7,000 to 10,000 cases in the United States. Many cases are due to craniopharyngioma and other nongenetic causes. The form inherited as an autosomal recessive is probably rare. (See also the rare X-linked form (<a href="/entry/312000">312000</a>).) Multiple cases in multiple sibships observed among the Hutterites, a religious isolate in the United States and Canada, indicate the recessive inheritance of panhypopituitarism (<a href="#16" class="mim-tip-reference" title="McKusick, V. A., Rimoin, D. L. <strong>General Tom Thumb and other midgets.</strong> Sci. Am. 217(1): 102-111, 1967.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6046325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6046325</a>] [<a href="https://doi.org/10.1038/scientificamerican0767-102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6046325">McKusick and Rimoin, 1967</a>). <a href="#15" class="mim-tip-reference" title="McArthur, R. G., Morgan, K., Phillips, J. A., III, Bala, M., Klassen, J. <strong>The natural history of familial hypopituitarism.</strong> Am. J. Med. Genet. 22: 553-566, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2998186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2998186</a>] [<a href="https://doi.org/10.1002/ajmg.1320220313" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2998186">McArthur et al. (1985)</a> studied the natural history of the Hutterite panhypopituitarism. The patients showed sequential loss of anterior pituitary tropic hormones. Three untreated sibs developed deficiency of growth hormone (GH; <a href="/entry/139250">139250</a>) and gonadotropin (see <a href="/entry/118850">118850</a>) in the first decade of life, with subsequent loss of thyroid-stimulating hormone (TSH; see <a href="/entry/188540">188540</a>) function, and finally development of ACTH deficiency (<a href="/entry/210400">210400</a>) in the third decade. In a second family, deficiency of GH, gonadotropins, and TSH were evident in the first decade. Southern blot analysis showed no abnormality of growth hormone genes; linkage studies excluded close linkage to HLA. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6046325+2998186" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Hanhart (<a href="#9" class="mim-tip-reference" title="Hanhart, E. <strong>Ueber heredodegenerativen Zwergwuchs mit dystrophia adiposogenitalis. An hand von Untersuchungen bei drei Sippen von proportionierten Zwergen.</strong> Arch. Klaus Stift. Vererbungsforsch. 1: 181-257, 1925."None>1925</a>, <a href="#10" class="mim-tip-reference" title="Hanhart, E. <strong>Die Rolle der Erbfaktoren bei den Stoerungen des Wachstums.</strong> Schweiz. Med. Wschr. 83: 198-203, 1953.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13076009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13076009</a>]" pmid="13076009">1953</a>) studied familial cases of dwarfism in the inbred population of certain areas of Switzerland and on the island of Veglia (Krk) in the Adriatic. <a href="#13" class="mim-tip-reference" title="Krzisnik, C., Kolacio, Z., Battelino, T., Brown, M., Parks, J. S., Laron, Z. <strong>The 'little people' of the Island of Krk - revisited: etiology of hypopituitarism revealed.</strong> J. Endocr. Genet. 1: 9-19, 1999."None>Krzisnik et al. (1999)</a> studied 6 affected patients on Krk. Clinical examination revealed dwarfism, obesity, dry wrinkled skin, and lack of sexual development. Hormonal investigations showed absence of growth hormone, unresponsive to growth hormone-releasing hormone (GHRH; <a href="/entry/139190">139190</a>), absence of luteinizing hormone (LH; <a href="/entry/118850">118850</a>) and follicle-stimulating hormone (FSH; <a href="/entry/136530">136530</a>), unresponsive to gonadotropin-releasing hormone (GnRH; <a href="/entry/152760">152760</a>), and absence of thyrotropin-stimulating hormone, unresponsive to thyrotropin-releasing hormone (TRH; <a href="/entry/613879">613879</a>). None of the patients were deficient in ACTH. In a follow-up study of patients from Krk, <a href="#12" class="mim-tip-reference" title="Krzisnik, C., Grguric, S., Cvijovic, K., Laron, Z. <strong>Longevity of the hypopituitary patients from the Island Krk: a follow-up study.</strong> Pediat. Endocr. Rev. 7: 357-362, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20679996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20679996</a>]" pmid="20679996">Krzisnik et al. (2010)</a> found that despite their long-lasting hormonal deficiencies, the patients live as long as 87 to 91 years, longer than the mean (71.1 to 79.1) reported for the Croatian population. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20679996+13076009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The nature of most panhypopituitarism as a congenital malformation with little indication of a mendelian basis is supported by the observation by <a href="#24" class="mim-tip-reference" title="Rosenfield, R. L., Root, A. W., Bongiovanni, A. M., Eberlein, W. R. <strong>Idiopathic anterior hypopituitarism in one of monozygotic twins.</strong> J. Pediat. 70: 115-117, 1967.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6017748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6017748</a>] [<a href="https://doi.org/10.1016/s0022-3476(67)80174-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6017748">Rosenfield et al. (1967)</a> of 16-year-old identical twins, one normal and one with panhypopituitarism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6017748" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Kirchhoff, H. W., Lehmann, W., Schaefer, U. <strong>Clinical, hereditary-biologic and constitutional studies of primordial dwarfs.</strong> Z. Kinderheilk. 75: 243-266, 1954.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13227184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13227184</a>]" pmid="13227184">Kirchhoff et al. (1954)</a> described 3 sibs with dwarfism who may have had panhypopituitarism, the oldest being almost 18 years old. <a href="#27" class="mim-tip-reference" title="Selye, H. <strong>Textbook of Endocrinology.</strong> Montreal: Univ. Montreal (pub.) 1947. P. 268."None>Selye (1947)</a> pictured 3 brothers, aged 25, 22, and 11 years, with panhypopituitarism. The cases described by <a href="#26" class="mim-tip-reference" title="Schmolck, (NI). <strong>Mehrfacher Zwergwuchs in verwandten Familien eines Hochgebirgstales.</strong> Virchows Arch. Path. Anat. 187: 105-111, 1907."None>Schmolck (1907)</a> may have been of the panhypopituitary type. <a href="#2" class="mim-tip-reference" title="Bailey, J. D., Bain, H. W., Thompson, M. W., Gagliardino, J. J., Martin, J. M. <strong>Etiological factors in idiopathic hypopituitary dwarfism. (Abstract)</strong> Pediat. Res. 1: 300-301, 1967."None>Bailey et al. (1967)</a> reported 2 families with a total of 5 affected. In one, the parents were first cousins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13227184" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#28" class="mim-tip-reference" title="Steiner, M. M., Boggs, J. D. <strong>Absence of pituitary gland, hypothyroidism, hypoadrenalism and hypogonadism in a 17-year-old dwarf.</strong> J. Clin. Endocr. 25: 1591-1598, 1965.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4284833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4284833</a>] [<a href="https://doi.org/10.1210/jcem-25-12-1591" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4284833">Steiner and Boggs (1965)</a> described brother and sister, offspring of first-cousin parents, with congenital absence of the pituitary, leading to hypothyroidism, hypoadrenalism, and hypogonadism. A third sib was probably also affected and died, presumably of hypoglycemia, in the newborn period. The sella turcica was normal in size. The disorder reported by <a href="#25" class="mim-tip-reference" title="Sadeghi-Nejad, A., Senior, B. <strong>A familial syndrome of isolated aplasia of the anterior pituitary. Diagnostic studies and treatment in the neonatal period.</strong> J. Pediat. 84: 79-84, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12119961/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12119961</a>] [<a href="https://doi.org/10.1016/s0022-3476(74)80557-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12119961">Sadeghi-Nejad and Senior (1974)</a> may be the same or an allelic disorder. A male newborn developed hypoglycemic convulsions. Diagnostic studies showed evidence of deficiency of thyrotropin, growth hormone, and prolactin (<a href="/entry/176760">176760</a>). The child thrived on replacement therapy. A female sib died in the first day of life with similar clinical findings and at autopsy showed absence of the anterior pituitary and atrophic adrenal glands. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12119961+4284833" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Pinto, G., Netchine, I., Sobrier, M. L., Brunelle, F., Souberbielle, J. C., Brauner, R. <strong>Pituitary stalk interruption syndrome: a clinical-biological-genetic assessment of its pathogenesis.</strong> J. Clin. Endocr. Metab. 82: 3450-3454, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9329385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9329385</a>] [<a href="https://doi.org/10.1210/jcem.82.10.4295" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9329385">Pinto et al. (1997)</a> noted that the finding of 'pituitary stalk interruption syndrome' (PSIS) by MRI is a clinical marker of permanent growth hormone deficiency. Some patients with PSIS have isolated GHD, whereas some have other pituitary hormone deficiencies. In a comparison of 16 patients with PSIS and isolated GHD with 35 patients with PSIS and other pituitary deficiencies, <a href="#20" class="mim-tip-reference" title="Pinto, G., Netchine, I., Sobrier, M. L., Brunelle, F., Souberbielle, J. C., Brauner, R. <strong>Pituitary stalk interruption syndrome: a clinical-biological-genetic assessment of its pathogenesis.</strong> J. Clin. Endocr. Metab. 82: 3450-3454, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9329385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9329385</a>] [<a href="https://doi.org/10.1210/jcem.82.10.4295" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9329385">Pinto et al. (1997)</a> concluded that most patients with GHD associated with multiple anterior pituitary abnormalities and PSIS had features suggestive of an antenatal origin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9329385" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Fluck, C., Deladoey, J., Rutishauser, K., Eble, A., Marti, U., Wu, W., Mullis, P. E. <strong>Phenotypic variability in familial combined pituitary hormone deficiency caused by a PROP1 gene mutation resulting in the substitution of arg to cys at codon 120 (R120C).</strong> J. Clin. Endocr. Metab. 83: 3727-3734, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9768691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9768691</a>] [<a href="https://doi.org/10.1210/jcem.83.10.5172" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9768691">Fluck et al. (1998)</a> followed 2 apparently unrelated consanguineous CPHD families (12 individuals total), with 5 affected individuals (3 males and 2 females), for more than 2 decades. The authors noted that there was variability in the phenotype, even among these patients who all carried the same mutation (R120C; <a href="/entry/601538#0001">601538.0001</a>). The age at diagnosis, ranging from 9 months to 8 years of age, was dependent on the severity of symptoms. Although in 1 patient TSH deficiency was the first symptom of the disorder, all patients exhibited severe growth retardation and failure to thrive, which was primarily (4 individuals) caused by GH deficiency. The secretion of the pituitary-derived hormones GH, PRL, TSH, LH, and FSH declined gradually with age, following a different pattern in each individual; therefore, the deficiencies developed over a variable period of time. All 5 patients entered puberty spontaneously, and the 2 females also experienced menarche before replacement therapy was necessary. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9768691" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Mendonca, B. B., Osorio, M. G. F., Latronico, A. C., Estefan, V., Lo, L. S. S., Arnhold, I. J. P. <strong>Longitudinal hormonal and pituitary imaging changes in two females with combined pituitary hormone deficiency due to deletion of A301,G302 in the PROP1 gene.</strong> J. Clin. Endocr. Metab. 84: 942-945, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10084575/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10084575</a>] [<a href="https://doi.org/10.1210/jcem.84.3.5537" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10084575">Mendonca et al. (1999)</a> studied 2 unrelated females with CPHD: patient 1 presented at 8.8 years with severe short stature, slightly enlarged sella turcica by x-ray, and a diffusely enlarged pituitary gland with hyperintense enhanced signal on T1 weighted image at coronal and sagittal views on magnetic resonance imaging (MRI). MRI repeated at age 15 years revealed a marked reduction of pituitary height. Patient 2 presented at 27 years with short stature, no pubertal development, normal sella turcica, and a pituitary gland of reduced size and normal intensity on MRI. Both patients had normal pituitary stalks and normally located neurohypophyses. Both had deficiencies of GH, TSH, PRL, LH, and FSH. Patient 1 had normal cortisol secretion at 8.8 years but by 16.6 years had developed partial cortisol deficiency, whereas patient 2 maintained normal cortisol secretion at 28.4 years. The authors concluded that a large sella turcica and an enlarged pituitary anterior lobe with hyperintense enhanced T1 signal on MRI suggests PROP1 deficiency; that pituitary morphology can change during follow-up of patients with PROP1 mutations; and that hormonal deficiencies associated with PROP1 mutations can include the adrenal axis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10084575" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Rosenbloom, A. L., Almonte, A. S., Brown, M. R., Fisher, D. A., Baumbach, L., Parks, J. S. <strong>Clinical and biochemical phenotype of familial anterior hypopituitarism from mutation of the PROP1 gene.</strong> J. Clin. Endocr. Metab. 84: 50-57, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9920061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9920061</a>] [<a href="https://doi.org/10.1210/jcem.84.1.5366" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9920061">Rosenbloom et al. (1999)</a> investigated a large Dominican kindred with PROP1 deficiency presenting as CPHD, the largest such family reported to that time. Eight patients, aged 17 to 40 years, in 2 sibships with possibly related mothers but no parental consanguinity, had marked short stature and were sexually immature. Affected individuals had similarities to and significant differences from patients with insulin-like growth factor (IGF1; <a href="/entry/147440">147440</a>) deficiency due to GH receptor (GHR; <a href="/entry/600946">600946</a>) deficiency (see Laron syndrome, <a href="/entry/262500">262500</a>), who have normal thyroid function and sexual maturation. The differences from patients with GHR deficiency included normal hand and foot length in 7 of 8 patients, normal arm span with relatively long legs, and persistence of extremely low levels of IGF1 into adulthood; similarities included the degree of growth failure, frequent but not uniform increased body weight for height or body mass index, and the presence of limited elbow extensibility and blue sclerae in 6 of 8 patients. While 3 patients had markedly increased sella turcica area for height age and bone age, the degree of sellar enlargement was variable in these 2 sibships. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9920061" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Congenital hypoplasia of the anterior pituitary gland is the most common MRI finding in patients with PROP1 mutations. <a href="#22" class="mim-tip-reference" title="Riepe, F. G., Partsch, C.-J., Blankenstein, O., Monig, H., Pfaffle, R. W., Sippell, W. G. <strong>Longitudinal imaging reveals pituitary enlargement preceding hypoplasia in two brothers with combined pituitary hormone deficiency attributable to PROP1 mutation.</strong> J. Clin. Endocr. Metab. 86: 4353-4357, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11549674/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11549674</a>] [<a href="https://doi.org/10.1210/jcem.86.9.7828" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11549674">Riepe et al. (2001)</a> studied 2 brothers with CPHD prospectively for almost 12 years with respect to variations in pituitary size. Both showed combined pituitary hormone deficiency of GH, TSH, PRL, and the gonadotropins FSH and LH, as is typical for PROP1 deficiency; retesting at ages 12 and 15 years, respectively, revealed developing insufficiency of ACTH and cortisol secretory capacity as well in both patients. Computerized tomography (CT) revealed an enlarged pituitary in the older brother at 3.5 years of age. Repeated MRI after 12 years showed a constant hypoplasia of the anterior pituitary lobe. Similarly, MRI of the younger brother showed a constant enlargement of the anterior pituitary gland until age 10 years. At the age of 11 years, the anterior pituitary was hypoplastic. The authors concluded that early pituitary enlargement may be the typical course in such patients in whom pituitary surgery is not indicated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11549674" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Reynaud, R., Chadli-Chaieb, M., Vallette-Kasic, S., Barlier, A., Sarles, J., Pellegrini-Bouiller, I., Enjalbert, A., Chaieb, L., Brue, T. <strong>A familial form of congenital hypopituitarism due to a PROP1 mutation in a large kindred: phenotypic and in vitro functional studies.</strong> J. Clin. Endocr. Metab. 89: 5779-5786, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15531542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15531542</a>] [<a href="https://doi.org/10.1210/jc.2003-032124" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15531542">Reynaud et al. (2004)</a> reported the natural history of hypopituitarism in a large Tunisian kindred including 29 subjects from the same consanguineous family. The index case was a 9-year-old girl with severe growth retardation due to complete GH deficiency and partial corticotroph, lactotroph, and thyrotroph deficiencies. MRI showed a hyperplastic anterior pituitary. Thirteen of the 28 relatives examined had hypopituitarism. In the 14 patients, previously untreated, height was -5.7 +/- 1.7 SD score, and puberty was spontaneously initiated in only 2 females. Complete GH deficiency was found in all 12 patients investigated, of whom 11 had thyrotroph deficiency; 8 of 10 investigated had corticotroph deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15531542" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To analyze the prevalence of adrenal insufficiency in patients with PROP1 defects and to characterize the temporal pattern of anterior pituitary failure, <a href="#3" class="mim-tip-reference" title="Bottner, A., Keller, E., Kratzsch, J., Stobbe, H., Weigel, J. F. W., Keller, A., Hirsch, W., Kiess, W., Blum, W. F., Pfaffle, R. W. <strong>PROP1 mutations cause progressive deterioration of anterior pituitary function including adrenal insufficiency: a longitudinal analysis.</strong> J. Clin. Endocr. Metab. 89: 5256-5265, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15472232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15472232</a>] [<a href="https://doi.org/10.1210/jc.2004-0661" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15472232">Bottner et al. (2004)</a> performed a retrospective longitudinal analysis of 9 patients with PROP1 mutations who were under medical supervision. All patients initially presented with growth failure at a mean age of 4.9 +/- 0.8 years. They were first diagnosed with GH and TSH deficiency, and replacement therapy was instituted at 6.1 +/- 1.1 and 6.8 +/- 1.2 years, respectively. All 7 patients who reached pubertal age required sex hormone substitution at 15.0 +/- 0.7 yr. Repeated functional testing of the anterior pituitary axes revealed a progressive decline with age in peak levels of GH, TSH, prolactin, and LH/FSH. All patients developed at least partial adrenal insufficiency with a gradual decline of the function of the pituitary adrenal axis and eventually required substitution with hydrocortisone at a mean age of 18.4 +/- 3.5 years. The authors concluded that anterior pituitary function in patients with PROP1 mutations deteriorates progressively and includes adrenal insufficiency as a feature of this condition, which has important clinical relevance in childhood and adolescence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15472232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Voutetakis, A., Argyropoulou, M., Sertedaki, A., Livadas, S., Xekouki, P., Maniati-Christidi, M., Bossis, I., Thalassinos, N., Patronas, N., Dacou-Voutetakis, C. <strong>Pituitary magnetic resonance imaging in 15 patients with Prop1 gene mutations: pituitary enlargement may originate from the intermediate lobe.</strong> J. Clin. Endocr. Metab. 89: 2200-2206, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15126542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15126542</a>] [<a href="https://doi.org/10.1210/jc.2003-031765" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15126542">Voutetakis et al. (2004)</a> used long-term MRI findings to characterize the morphologic abnormalities of the pituitary gland in 15 patients with CPHD caused by PROP1 gene mutations. Small pituitary gland was detected in 7 patients (25.2 +/- 14.4 years of age), normal pituitary size in 3 patients (10.2 +/- 5.8 years of age), and pituitary enlargement in 5 patients (6.5 +/- 2.7 years of age). The pituitary enlargement consisted of a nonenhancing mass lesion interposed between the normally enhancing anterior lobe and the neurohypophysis. The pituitary stalk was displaced anteriorly, whereas the neurohypophysis was orthotopic, displaying a normal signal. Spontaneous regression of the mass lesion with normalization of the pituitary stalk position was observed in 3 patients. The authors concluded that while a small pituitary gland is usually observed in older subjects, a significant number of young patients with PROP1 gene mutations demonstrate pituitary enlargement with subsequent regression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15126542" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="inheritance" class="mim-anchor"></a>
|
|
<h4 href="#mimInheritanceFold" id="mimInheritanceToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimInheritanceToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimInheritanceFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>The transmisssion pattern of CPHD2 in the families reported by <a href="#31" class="mim-tip-reference" title="Wu, W., Cogan, J. D., Pfaffle, R. W., Dasen, J. S., Frisch, H., O'Connell, S. M., Flynn, S. E., Brown, M. R., Mullis, P. E., Parks, J. S., Phillips, J. A., III, Rosenfeld, M. G. <strong>Mutations in PROP1 cause familial combined pituitary hormone deficiency.</strong> Nature Genet. 18: 147-149, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9462743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9462743</a>] [<a href="https://doi.org/10.1038/ng0298-147" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9462743">Wu et al. (1998)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9462743" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 4 CPHD families, who showed deficiency of growth hormone (GH; <a href="/entry/139250">139250</a>), prolactin (PRL; <a href="/entry/176760">176760</a>), thyrotropin (TSH; see <a href="/entry/188540">188540</a>), luteinizing hormone (LH; see <a href="/entry/152780">152780</a>), and follicle-stimulating hormone (FSH; see <a href="/entry/136530">136530</a>), but normal levels of adrenocorticotrophic hormone (ACTH; see <a href="/entry/176830">176830</a>), <a href="#31" class="mim-tip-reference" title="Wu, W., Cogan, J. D., Pfaffle, R. W., Dasen, J. S., Frisch, H., O'Connell, S. M., Flynn, S. E., Brown, M. R., Mullis, P. E., Parks, J. S., Phillips, J. A., III, Rosenfeld, M. G. <strong>Mutations in PROP1 cause familial combined pituitary hormone deficiency.</strong> Nature Genet. 18: 147-149, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9462743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9462743</a>] [<a href="https://doi.org/10.1038/ng0298-147" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9462743">Wu et al. (1998)</a> identified homozygosity or compound heterozygosity for inactivating mutations of the PROP1 gene (<a href="/entry/601538#0001">601538.0001</a>-<a href="/entry/601538#0003">601538.0003</a>, respectively). In contrast to individuals with CPHD1 (<a href="/entry/613038">613038</a>), who have mutations in the human homolog of the mouse Pit1 gene, POU1F1 (<a href="/entry/173110">173110</a>), those with PROP1 mutations cannot produce LH or FSH at a sufficient level and do not enter puberty spontaneously. These results identified a major cause of combined pituitary hormone deficiency in humans and suggested a direct or indirect role for PROP1 in the ontogenesis of pituitary gonadotropes, as well as somatotropes, lactotropes, and caudomedial thyrotropes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9462743" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 5 affected individuals from 2 apparently unrelated consanguineous CPHD families, <a href="#6" class="mim-tip-reference" title="Fluck, C., Deladoey, J., Rutishauser, K., Eble, A., Marti, U., Wu, W., Mullis, P. E. <strong>Phenotypic variability in familial combined pituitary hormone deficiency caused by a PROP1 gene mutation resulting in the substitution of arg to cys at codon 120 (R120C).</strong> J. Clin. Endocr. Metab. 83: 3727-3734, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9768691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9768691</a>] [<a href="https://doi.org/10.1210/jcem.83.10.5172" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9768691">Fluck et al. (1998)</a> identified homozygosity for the R120C mutation in the PROP1 gene (<a href="/entry/601538#0001">601538.0001</a>). The authors noted that there was variability in age of onset and severity of symptoms, even among these patients with the same mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9768691" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 individuals with panhypopituitarism from the isolated community on the Island of Krk, <a href="#13" class="mim-tip-reference" title="Krzisnik, C., Kolacio, Z., Battelino, T., Brown, M., Parks, J. S., Laron, Z. <strong>The 'little people' of the Island of Krk - revisited: etiology of hypopituitarism revealed.</strong> J. Endocr. Genet. 1: 9-19, 1999."None>Krzisnik et al. (1999)</a> identified homozygosity for a frameshift mutation in the PROP1 gene (<a href="/entry/601538#0014">601538.0014</a>).</p><p>PROP1 deficiency should be considered as a potential cause of all familial cases of CPHD. In 10 independently ascertained CPHD kindreds, <a href="#4" class="mim-tip-reference" title="Cogan, J. D., Wu, W., Phillips, J. A., III, Arnhold, I. J. P., Agapito, A., Fofanova, O. V., Osorio, M. G. F., Bircan, I., Moreno, A., Mendonca, B. B. <strong>The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency.</strong> J. Clin. Endocr. Metab. 83: 3346-3349, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9745452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9745452</a>] [<a href="https://doi.org/10.1210/jcem.83.9.5142" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9745452">Cogan et al. (1998)</a> found that 55% (11 of 20) of the PROP1 alleles were 301delAG (<a href="/entry/602538#0002">602538.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9745452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Fofanova, O., Takamura, N., Kinoshita, E., Parks, J. S., Brown, M. R., Peterkova, V. A., Evgrafov, O. V., Goncharov, N. P., Bulatov, A. A., Dedov, I. I., Yamashita, S. <strong>Compound heterozygous deletion of the PROP-1 gene in children with combined pituitary hormone deficiency.</strong> J. Clin. Endocr. Metab. 83: 2601-2604, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9661653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9661653</a>] [<a href="https://doi.org/10.1210/jcem.83.7.5094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9661653">Fofanova et al. (1998)</a> analyzed the POU1F1 (<a href="/entry/173110">173110</a>) and PROP1 genes in 14 Russian children with CPHD, 7 unrelated and 7 from 4 families, who had complete GH and complete or partial PRL and TSH deficiencies. A missense mutation in POU1F1 was identified in 1 patient, and 8 other patients were found to be homozygous or compound heterozygous for 2 different deletions in the PROP1 gene, 149delGA (<a href="/entry/601538#0004">601538.0004</a>) and 296delGA (<a href="/entry/601538#0005">601538.0005</a>), respectively. All parents were of normal stature and each was heterozygous for a wildtype allele and 1 of the deletions, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9661653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated females with CPHD involving GH, TSH, PRL, LH, and FSH, 1 of whom also had partial cortisol deficiency, <a href="#17" class="mim-tip-reference" title="Mendonca, B. B., Osorio, M. G. F., Latronico, A. C., Estefan, V., Lo, L. S. S., Arnhold, I. J. P. <strong>Longitudinal hormonal and pituitary imaging changes in two females with combined pituitary hormone deficiency due to deletion of A301,G302 in the PROP1 gene.</strong> J. Clin. Endocr. Metab. 84: 942-945, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10084575/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10084575</a>] [<a href="https://doi.org/10.1210/jcem.84.3.5537" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10084575">Mendonca et al. (1999)</a> identified homozygosity for a 2-bp deletion in the PROP1 gene (<a href="/entry/601538#0002">601538.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10084575" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 8 patients from a large Dominican CPHD kindred, <a href="#23" class="mim-tip-reference" title="Rosenbloom, A. L., Almonte, A. S., Brown, M. R., Fisher, D. A., Baumbach, L., Parks, J. S. <strong>Clinical and biochemical phenotype of familial anterior hypopituitarism from mutation of the PROP1 gene.</strong> J. Clin. Endocr. Metab. 84: 50-57, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9920061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9920061</a>] [<a href="https://doi.org/10.1210/jcem.84.1.5366" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9920061">Rosenbloom et al. (1999)</a> identified homozygosity for the 296delGA mutation in the PROP1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9920061" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 10 CPHD patients from a large Brazilian kindred, 9 of whom were born of consanguineous marriages, <a href="#19" class="mim-tip-reference" title="Pernasetti, F., Toledo, S. P. A., Vasilyev, V. V., Hayashida, C. Y., Cogan, J. D., Ferrari, C., Lourenco, D. M., Mellon, P. L. <strong>Impaired adrenocorticotropin-adrenal axis in combined pituitary hormone deficiency caused by a two-base pair deletion (301-302delAG) in the prophet of Pit-1 gene.</strong> J. Clin. Endocr. Metab. 85: 390-397, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10634415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10634415</a>] [<a href="https://doi.org/10.1210/jcem.85.1.6324" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10634415">Pernasetti et al. (2000)</a> identified homozygosity for a 2-bp deletion in the PROP1 gene (301delAG; <a href="/entry/601538#0002">601538.0002</a>). All affected patients presented complete absence of puberty and low GH, PRL, TSH, LH, and FSH associated with severe hypoplasia of the pituitary gland, as seen by MRI. The authors observed ACTH/cortisol insufficiency in 5 of 6 of the older patients and in 1 11-year-old patient, and suggested that the phenotype of this mutation includes late-onset adrenal insufficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10634415" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Agarwal, G., Bhatia, V., Cook, S., Thomas, P. Q. <strong>Adrenocorticotropin deficiency in combined pituitary hormone deficiency patients homozygous for a novel PROP1 deletion.</strong> J. Clin. Endocr. Metab. 85: 4556-4561, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11134108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11134108</a>] [<a href="https://doi.org/10.1210/jcem.85.12.7013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11134108">Agarwal et al. (2000)</a> analyzed the PROP1 gene in a large consanguineous Indian pedigree with CPHD and identified homozygosity for a 13-bp deletion in affected individuals, predicted to generate a null allele (<a href="/entry/601538#0007">601538.0007</a>). Severe cortisol deficiency was observed in 2 patients in this family, suggesting a role for PROP1 in the differentiation and/or maintenance of corticotroph cells in the mature anterior pituitary. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11134108" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#29" class="mim-tip-reference" title="Vallette-Kasic, S., Barlier, A., Teinturier, C., Diaz, A., Manavela, M., Berthezene, F., Bouchard, P., Chaussain, J. L., Brauner, R., Pellegrini-Bouiller, I., Jaquet, P., Enjalbert, A., Brue, T. <strong>PROP1 gene screening in patients with multiple pituitary hormone deficiency reveals two sites of hypermutability and a high incidence of corticotroph deficiency.</strong> J. Clin. Endocr. Metab. 86: 4529-4535, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11549703/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11549703</a>] [<a href="https://doi.org/10.1210/jcem.86.9.7811" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11549703">Vallette-Kasic et al. (2001)</a> screened the PROP1 gene in 23 CPHD patients and identified homozygosity or compound heterozygosity for 4 different mutations in 9 patients from 8 unrelated families. All mutations were located in exon 2 and affected only 2 different sites (see <a href="/entry/601538#0005">601538.0005</a> and <a href="/entry/601538#0009">601538.0009</a>-<a href="/entry/601538#0011">601538.0011</a>). All of the patients were born to unaffected parents, and consanguinity was documented in 2 patients. They had complete GH, LH-FSH, and TSH deficiencies, and normal basal levels of PRL with blunted PRL response to TRH; delayed ACTH deficiency was diagnosed in 4 patients. All had complete hypogonadotrophic hypogonadism and none entered puberty spontaneously. MRI showed a hypoplastic anterior pituitary 7 patients and in 2 patients, there was initial hyperplasia with subsequent hypoplasia on a later study; 2 patients also showed an enlarged sella turcica. <a href="#29" class="mim-tip-reference" title="Vallette-Kasic, S., Barlier, A., Teinturier, C., Diaz, A., Manavela, M., Berthezene, F., Bouchard, P., Chaussain, J. L., Brauner, R., Pellegrini-Bouiller, I., Jaquet, P., Enjalbert, A., Brue, T. <strong>PROP1 gene screening in patients with multiple pituitary hormone deficiency reveals two sites of hypermutability and a high incidence of corticotroph deficiency.</strong> J. Clin. Endocr. Metab. 86: 4529-4535, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11549703/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11549703</a>] [<a href="https://doi.org/10.1210/jcem.86.9.7811" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11549703">Vallette-Kasic et al. (2001)</a> stated that, in keeping with previous reports, they found no correlation between phenotype and genotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11549703" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 brothers with CPHD who both had early hyperplasia and later hypoplasia of the anterior pituitary by MRI, <a href="#22" class="mim-tip-reference" title="Riepe, F. G., Partsch, C.-J., Blankenstein, O., Monig, H., Pfaffle, R. W., Sippell, W. G. <strong>Longitudinal imaging reveals pituitary enlargement preceding hypoplasia in two brothers with combined pituitary hormone deficiency attributable to PROP1 mutation.</strong> J. Clin. Endocr. Metab. 86: 4353-4357, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11549674/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11549674</a>] [<a href="https://doi.org/10.1210/jcem.86.9.7828" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11549674">Riepe et al. (2001)</a> identified compound heterozygosity for inactivating mutations in the PROP1 gene, 301delAG and 150delA (<a href="/entry/601538#0008">601538.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11549674" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The panhypopituitarism in the Hutterite cases reported by <a href="#16" class="mim-tip-reference" title="McKusick, V. A., Rimoin, D. L. <strong>General Tom Thumb and other midgets.</strong> Sci. Am. 217(1): 102-111, 1967.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6046325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6046325</a>] [<a href="https://doi.org/10.1038/scientificamerican0767-102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6046325">McKusick and Rimoin (1967)</a> were shown to be due to the common 2-bp deletion (301-302delAG) in the PROP1 gene (<a href="/entry/601538#0002">601538.0002</a>) (<a href="#18" class="mim-tip-reference" title="Mosely, C. T., Phillips, J. A., III, Rimoin, D. L. <strong>Genetic disorders of the pituitary gland. In: Rimoin, D. L.; Connor J. M.; Pyeritz, R. E.; Korf, B. R. (eds.): Emery and Rimoin's Principles and Practices of Medical Genetics. (4th ed.)</strong> London: Churchill Livingston (pub.) 2002. P. 2153. Note: Fig. 80.3."None>Mosely et al., 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6046325" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Reynaud, R., Chadli-Chaieb, M., Vallette-Kasic, S., Barlier, A., Sarles, J., Pellegrini-Bouiller, I., Enjalbert, A., Chaieb, L., Brue, T. <strong>A familial form of congenital hypopituitarism due to a PROP1 mutation in a large kindred: phenotypic and in vitro functional studies.</strong> J. Clin. Endocr. Metab. 89: 5779-5786, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15531542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15531542</a>] [<a href="https://doi.org/10.1210/jc.2003-032124" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15531542">Reynaud et al. (2004)</a> studied 3 brothers with CPHD from a consanguineous family of Tunisian descent. The brothers had been referred for cryptorchidism and/or delayed puberty, and initial investigations revealed hypogonadotropic hypogonadism. One of the patients had psychomotor retardation, intracranial hypertension, and minor renal malformations. The brothers reached normal adult height and developed GH and TSH deficiencies after age 30. <a href="#21" class="mim-tip-reference" title="Reynaud, R., Chadli-Chaieb, M., Vallette-Kasic, S., Barlier, A., Sarles, J., Pellegrini-Bouiller, I., Enjalbert, A., Chaieb, L., Brue, T. <strong>A familial form of congenital hypopituitarism due to a PROP1 mutation in a large kindred: phenotypic and in vitro functional studies.</strong> J. Clin. Endocr. Metab. 89: 5779-5786, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15531542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15531542</a>] [<a href="https://doi.org/10.1210/jc.2003-032124" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15531542">Reynaud et al. (2004)</a> identified homozygosity for a nonsense mutation in the PROP1 gene (W194X; <a href="/entry/601538#0010">601538.0010</a>) in the affected brothers, and concluded that PROP1 mutations should be considered among the genetic causes of initially isolated hypogonadotropic hypogonadism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15531542" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="pathogenesis" class="mim-anchor"></a>
|
|
<h4 href="#mimPathogenesisFold" id="mimPathogenesisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimPathogenesisToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Pathogenesis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimPathogenesisFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Inactivating mutations in PROP1 perturb ontogenesis of pituitary gonadotropes, somatotropes, lactotropes, and thyrotropes. These developmental defects result in deficiencies of PRL, LH, FSH, GH, or TSH.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="clinicalManagement" class="mim-anchor"></a>
|
|
<h4 href="#mimClinicalManagementFold" id="mimClinicalManagementToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimClinicalManagementToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Clinical Management</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimClinicalManagementFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Individuals with PROP1 mutations that cause GH and TSH deficiencies respond to GH and thyroid hormone replacement. Those with PROP1 mutations that cannot produce luteinizing or follicle-stimulating hormone at a sufficient level may not enter puberty spontaneously which may require gonadotropin replacement. Some older affected individuals have been reported to develop adrenal insufficiency in their third to fifth decades due to ACTH deficiency (<a href="/entry/202200">202200</a>) (<a href="#6" class="mim-tip-reference" title="Fluck, C., Deladoey, J., Rutishauser, K., Eble, A., Marti, U., Wu, W., Mullis, P. E. <strong>Phenotypic variability in familial combined pituitary hormone deficiency caused by a PROP1 gene mutation resulting in the substitution of arg to cys at codon 120 (R120C).</strong> J. Clin. Endocr. Metab. 83: 3727-3734, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9768691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9768691</a>] [<a href="https://doi.org/10.1210/jcem.83.10.5172" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9768691">Fluck et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9768691" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Lee, J. K., Zhu, Y.-S., Cordero, J. J., Cai, L.-Q., Labour, I., Herrera, C., Imperato-McGinley, J. <strong>Long-term growth hormone therapy in adult results in significant linear growth in siblings with a PROP-1 gene mutation.</strong> J. Clin. Endocr. Metab. 89: 4850-4856, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15472175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15472175</a>] [<a href="https://doi.org/10.1210/jc.2003-031816" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15472175">Lee et al. (2004)</a> reported 3 adult sibs, aged 18 to 25 years, with short stature, hypothyroidism, and lack of pubertal maturation, who were homozygous for the 301delAG PROP1 deletion (<a href="/entry/601538#0002">601538.0002</a>). They treated them in adulthood with GH for 4 to 5 years and thyroid replacement before sex steroid replacement therapy. Despite delay in treatment and fairly advanced bone age, all responded to these therapies with a dramatic increase in linear growth. The authors concluded the substantial linear growth in adult sibs with a PROP1 mutation illustrates that despite an advanced bone age, linear growth potential remains in adulthood in the setting of sex steroid deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15472175" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="seeAlso" class="mim-anchor"></a>
|
|
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<a href="#Ferrier1969" class="mim-tip-reference" title="Ferrier, P. E. <strong>Congenital absence or hypoplasia of the endocrine glands.</strong> J. Genet. Hum. 17: 325-347, 1969.">Ferrier (1969)</a>; <a href="#Fraser1964" class="mim-tip-reference" title="Fraser, G. R. <strong>Studies in isolates.</strong> J. Genet. Hum. 13: 32-46, 1964.">Fraser (1964)</a>; <a href="#Zergollern1971" class="mim-tip-reference" title="Zergollern, L. <strong>A follow-up on Hanhart's dwarfs of Krk.</strong> Birth Defects Orig. Art. Ser. VII(6): 28-32, 1971.">Zergollern (1971)</a>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="references"class="mim-anchor"></a>
|
|
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Agarwal2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Agarwal, G., Bhatia, V., Cook, S., Thomas, P. Q.
|
|
<strong>Adrenocorticotropin deficiency in combined pituitary hormone deficiency patients homozygous for a novel PROP1 deletion.</strong>
|
|
J. Clin. Endocr. Metab. 85: 4556-4561, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11134108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11134108</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11134108" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.85.12.7013" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Bailey1967" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bailey, J. D., Bain, H. W., Thompson, M. W., Gagliardino, J. J., Martin, J. M.
|
|
<strong>Etiological factors in idiopathic hypopituitary dwarfism. (Abstract)</strong>
|
|
Pediat. Res. 1: 300-301, 1967.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Bottner2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bottner, A., Keller, E., Kratzsch, J., Stobbe, H., Weigel, J. F. W., Keller, A., Hirsch, W., Kiess, W., Blum, W. F., Pfaffle, R. W.
|
|
<strong>PROP1 mutations cause progressive deterioration of anterior pituitary function including adrenal insufficiency: a longitudinal analysis.</strong>
|
|
J. Clin. Endocr. Metab. 89: 5256-5265, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15472232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15472232</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15472232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2004-0661" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Cogan1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cogan, J. D., Wu, W., Phillips, J. A., III, Arnhold, I. J. P., Agapito, A., Fofanova, O. V., Osorio, M. G. F., Bircan, I., Moreno, A., Mendonca, B. B.
|
|
<strong>The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency.</strong>
|
|
J. Clin. Endocr. Metab. 83: 3346-3349, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9745452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9745452</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9745452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.83.9.5142" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Ferrier1969" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ferrier, P. E.
|
|
<strong>Congenital absence or hypoplasia of the endocrine glands.</strong>
|
|
J. Genet. Hum. 17: 325-347, 1969.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4918329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4918329</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4918329" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Fluck1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fluck, C., Deladoey, J., Rutishauser, K., Eble, A., Marti, U., Wu, W., Mullis, P. E.
|
|
<strong>Phenotypic variability in familial combined pituitary hormone deficiency caused by a PROP1 gene mutation resulting in the substitution of arg to cys at codon 120 (R120C).</strong>
|
|
J. Clin. Endocr. Metab. 83: 3727-3734, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9768691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9768691</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9768691" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.83.10.5172" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Fofanova1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fofanova, O., Takamura, N., Kinoshita, E., Parks, J. S., Brown, M. R., Peterkova, V. A., Evgrafov, O. V., Goncharov, N. P., Bulatov, A. A., Dedov, I. I., Yamashita, S.
|
|
<strong>Compound heterozygous deletion of the PROP-1 gene in children with combined pituitary hormone deficiency.</strong>
|
|
J. Clin. Endocr. Metab. 83: 2601-2604, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9661653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9661653</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9661653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.83.7.5094" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Fraser1964" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fraser, G. R.
|
|
<strong>Studies in isolates.</strong>
|
|
J. Genet. Hum. 13: 32-46, 1964.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14192062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14192062</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14192062" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Hanhart1925" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hanhart, E.
|
|
<strong>Ueber heredodegenerativen Zwergwuchs mit dystrophia adiposogenitalis. An hand von Untersuchungen bei drei Sippen von proportionierten Zwergen.</strong>
|
|
Arch. Klaus Stift. Vererbungsforsch. 1: 181-257, 1925.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Hanhart1953" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hanhart, E.
|
|
<strong>Die Rolle der Erbfaktoren bei den Stoerungen des Wachstums.</strong>
|
|
Schweiz. Med. Wschr. 83: 198-203, 1953.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13076009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13076009</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13076009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Kirchhoff1954" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kirchhoff, H. W., Lehmann, W., Schaefer, U.
|
|
<strong>Clinical, hereditary-biologic and constitutional studies of primordial dwarfs.</strong>
|
|
Z. Kinderheilk. 75: 243-266, 1954.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13227184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13227184</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13227184" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Krzisnik2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Krzisnik, C., Grguric, S., Cvijovic, K., Laron, Z.
|
|
<strong>Longevity of the hypopituitary patients from the Island Krk: a follow-up study.</strong>
|
|
Pediat. Endocr. Rev. 7: 357-362, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20679996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20679996</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20679996" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Krzisnik1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Krzisnik, C., Kolacio, Z., Battelino, T., Brown, M., Parks, J. S., Laron, Z.
|
|
<strong>The 'little people' of the Island of Krk - revisited: etiology of hypopituitarism revealed.</strong>
|
|
J. Endocr. Genet. 1: 9-19, 1999.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Lee2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lee, J. K., Zhu, Y.-S., Cordero, J. J., Cai, L.-Q., Labour, I., Herrera, C., Imperato-McGinley, J.
|
|
<strong>Long-term growth hormone therapy in adult results in significant linear growth in siblings with a PROP-1 gene mutation.</strong>
|
|
J. Clin. Endocr. Metab. 89: 4850-4856, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15472175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15472175</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15472175" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2003-031816" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="McArthur1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McArthur, R. G., Morgan, K., Phillips, J. A., III, Bala, M., Klassen, J.
|
|
<strong>The natural history of familial hypopituitarism.</strong>
|
|
Am. J. Med. Genet. 22: 553-566, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2998186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2998186</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2998186" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1320220313" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="McKusick1967" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McKusick, V. A., Rimoin, D. L.
|
|
<strong>General Tom Thumb and other midgets.</strong>
|
|
Sci. Am. 217(1): 102-111, 1967.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6046325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6046325</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6046325" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/scientificamerican0767-102" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Mendonca1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mendonca, B. B., Osorio, M. G. F., Latronico, A. C., Estefan, V., Lo, L. S. S., Arnhold, I. J. P.
|
|
<strong>Longitudinal hormonal and pituitary imaging changes in two females with combined pituitary hormone deficiency due to deletion of A301,G302 in the PROP1 gene.</strong>
|
|
J. Clin. Endocr. Metab. 84: 942-945, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10084575/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10084575</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10084575" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.84.3.5537" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Mosely2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mosely, C. T., Phillips, J. A., III, Rimoin, D. L.
|
|
<strong>Genetic disorders of the pituitary gland. In: Rimoin, D. L.; Connor J. M.; Pyeritz, R. E.; Korf, B. R. (eds.): Emery and Rimoin's Principles and Practices of Medical Genetics. (4th ed.)</strong>
|
|
London: Churchill Livingston (pub.) 2002. P. 2153. Note: Fig. 80.3.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Pernasetti2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pernasetti, F., Toledo, S. P. A., Vasilyev, V. V., Hayashida, C. Y., Cogan, J. D., Ferrari, C., Lourenco, D. M., Mellon, P. L.
|
|
<strong>Impaired adrenocorticotropin-adrenal axis in combined pituitary hormone deficiency caused by a two-base pair deletion (301-302delAG) in the prophet of Pit-1 gene.</strong>
|
|
J. Clin. Endocr. Metab. 85: 390-397, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10634415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10634415</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10634415" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.85.1.6324" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Pinto1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pinto, G., Netchine, I., Sobrier, M. L., Brunelle, F., Souberbielle, J. C., Brauner, R.
|
|
<strong>Pituitary stalk interruption syndrome: a clinical-biological-genetic assessment of its pathogenesis.</strong>
|
|
J. Clin. Endocr. Metab. 82: 3450-3454, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9329385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9329385</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9329385" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.82.10.4295" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Reynaud2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Reynaud, R., Chadli-Chaieb, M., Vallette-Kasic, S., Barlier, A., Sarles, J., Pellegrini-Bouiller, I., Enjalbert, A., Chaieb, L., Brue, T.
|
|
<strong>A familial form of congenital hypopituitarism due to a PROP1 mutation in a large kindred: phenotypic and in vitro functional studies.</strong>
|
|
J. Clin. Endocr. Metab. 89: 5779-5786, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15531542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15531542</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15531542" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2003-032124" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Riepe2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Riepe, F. G., Partsch, C.-J., Blankenstein, O., Monig, H., Pfaffle, R. W., Sippell, W. G.
|
|
<strong>Longitudinal imaging reveals pituitary enlargement preceding hypoplasia in two brothers with combined pituitary hormone deficiency attributable to PROP1 mutation.</strong>
|
|
J. Clin. Endocr. Metab. 86: 4353-4357, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11549674/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11549674</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11549674" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.86.9.7828" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Rosenbloom1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rosenbloom, A. L., Almonte, A. S., Brown, M. R., Fisher, D. A., Baumbach, L., Parks, J. S.
|
|
<strong>Clinical and biochemical phenotype of familial anterior hypopituitarism from mutation of the PROP1 gene.</strong>
|
|
J. Clin. Endocr. Metab. 84: 50-57, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9920061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9920061</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9920061" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.84.1.5366" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Rosenfield1967" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rosenfield, R. L., Root, A. W., Bongiovanni, A. M., Eberlein, W. R.
|
|
<strong>Idiopathic anterior hypopituitarism in one of monozygotic twins.</strong>
|
|
J. Pediat. 70: 115-117, 1967.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6017748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6017748</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6017748" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0022-3476(67)80174-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Sadeghi-Nejad1974" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sadeghi-Nejad, A., Senior, B.
|
|
<strong>A familial syndrome of isolated aplasia of the anterior pituitary. Diagnostic studies and treatment in the neonatal period.</strong>
|
|
J. Pediat. 84: 79-84, 1974.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12119961/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12119961</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12119961" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0022-3476(74)80557-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Schmolck1907" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schmolck, (NI).
|
|
<strong>Mehrfacher Zwergwuchs in verwandten Familien eines Hochgebirgstales.</strong>
|
|
Virchows Arch. Path. Anat. 187: 105-111, 1907.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Selye1947" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Selye, H.
|
|
<strong>Textbook of Endocrinology.</strong>
|
|
Montreal: Univ. Montreal (pub.) 1947. P. 268.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Steiner1965" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Steiner, M. M., Boggs, J. D.
|
|
<strong>Absence of pituitary gland, hypothyroidism, hypoadrenalism and hypogonadism in a 17-year-old dwarf.</strong>
|
|
J. Clin. Endocr. 25: 1591-1598, 1965.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4284833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4284833</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4284833" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem-25-12-1591" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Vallette-Kasic2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vallette-Kasic, S., Barlier, A., Teinturier, C., Diaz, A., Manavela, M., Berthezene, F., Bouchard, P., Chaussain, J. L., Brauner, R., Pellegrini-Bouiller, I., Jaquet, P., Enjalbert, A., Brue, T.
|
|
<strong>PROP1 gene screening in patients with multiple pituitary hormone deficiency reveals two sites of hypermutability and a high incidence of corticotroph deficiency.</strong>
|
|
J. Clin. Endocr. Metab. 86: 4529-4535, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11549703/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11549703</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11549703" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.86.9.7811" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Voutetakis2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Voutetakis, A., Argyropoulou, M., Sertedaki, A., Livadas, S., Xekouki, P., Maniati-Christidi, M., Bossis, I., Thalassinos, N., Patronas, N., Dacou-Voutetakis, C.
|
|
<strong>Pituitary magnetic resonance imaging in 15 patients with Prop1 gene mutations: pituitary enlargement may originate from the intermediate lobe.</strong>
|
|
J. Clin. Endocr. Metab. 89: 2200-2206, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15126542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15126542</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15126542" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2003-031765" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Wu1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wu, W., Cogan, J. D., Pfaffle, R. W., Dasen, J. S., Frisch, H., O'Connell, S. M., Flynn, S. E., Brown, M. R., Mullis, P. E., Parks, J. S., Phillips, J. A., III, Rosenfeld, M. G.
|
|
<strong>Mutations in PROP1 cause familial combined pituitary hormone deficiency.</strong>
|
|
Nature Genet. 18: 147-149, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9462743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9462743</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9462743" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0298-147" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Zergollern1971" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zergollern, L.
|
|
<strong>A follow-up on Hanhart's dwarfs of Krk.</strong>
|
|
Birth Defects Orig. Art. Ser. VII(6): 28-32, 1971.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5173178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5173178</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5173178" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Carol A. Bocchini - updated : 05/23/2020
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Marla J. F. O'Neill - updated : 10/2/2009<br>John A. Phillips, III - updated : 2/21/2008<br>John A. Phillips, III - updated : 4/9/2007<br>John A. Phillips, III - updated : 4/7/2006<br>Victor A. McKusick - updated : 12/5/2005<br>Victor A. McKusick - updated : 5/26/2000<br>John A. Phillips, III - updated : 12/25/1997
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/4/1986
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 07/17/2024
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 09/16/2020<br>carol : 05/23/2020<br>carol : 09/09/2016<br>carol : 07/14/2016<br>carol : 7/9/2016<br>carol : 5/13/2014<br>joanna : 6/4/2013<br>terry : 9/9/2010<br>terry : 5/11/2010<br>terry : 5/11/2010<br>carol : 10/2/2009<br>alopez : 5/8/2009<br>ckniffin : 4/30/2008<br>carol : 2/21/2008<br>carol : 2/21/2008<br>carol : 4/9/2007<br>alopez : 4/7/2006<br>alopez : 1/6/2006<br>terry : 12/5/2005<br>carol : 1/26/2005<br>alopez : 5/30/2000<br>joanna : 5/26/2000<br>alopez : 1/26/1998<br>alopez : 1/24/1998<br>terry : 7/18/1994<br>mimadm : 4/17/1994<br>warfield : 3/9/1994<br>carol : 3/1/1993<br>carol : 2/4/1993<br>supermim : 3/17/1992
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="container visible-print-block">
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
<div class="col-md-8 col-md-offset-1">
|
|
|
|
<div>
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
<strong>#</strong> 262600
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
PITUITARY HORMONE DEFICIENCY, COMBINED, 2; CPHD2
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div >
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
PANHYPOPITUITARISM<br />
|
|
ATELIOTIC DWARFISM WITH HYPOGONADISM<br />
|
|
PITUITARY DWARFISM III<br />
|
|
HANHART DWARFISM
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 32390006;
|
|
|
|
|
|
<strong>ICD10CM:</strong> E23.0;
|
|
|
|
|
|
<strong>ICD9CM:</strong> 253.2;
|
|
|
|
|
|
<strong>ORPHA:</strong> 90695, 95494;
|
|
|
|
|
|
<strong>DO:</strong> 0061020;
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
5q35.3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Pituitary hormone deficiency, combined, 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
262600
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
PROP1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
601538
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because combined pituitary hormone deficiency-2 (CPHD2) is caused by homozygous or compound heterozygous mutation in the PROP1 gene (601538) on chromosome 5q35.</p><p>For discussion of phenotypic and genetic heterogeneity of combined pituitary hormone deficiency, see CPHD1 (613038).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Panhypopituitary dwarfism is not excessively rare, there probably being 7,000 to 10,000 cases in the United States. Many cases are due to craniopharyngioma and other nongenetic causes. The form inherited as an autosomal recessive is probably rare. (See also the rare X-linked form (312000).) Multiple cases in multiple sibships observed among the Hutterites, a religious isolate in the United States and Canada, indicate the recessive inheritance of panhypopituitarism (McKusick and Rimoin, 1967). McArthur et al. (1985) studied the natural history of the Hutterite panhypopituitarism. The patients showed sequential loss of anterior pituitary tropic hormones. Three untreated sibs developed deficiency of growth hormone (GH; 139250) and gonadotropin (see 118850) in the first decade of life, with subsequent loss of thyroid-stimulating hormone (TSH; see 188540) function, and finally development of ACTH deficiency (210400) in the third decade. In a second family, deficiency of GH, gonadotropins, and TSH were evident in the first decade. Southern blot analysis showed no abnormality of growth hormone genes; linkage studies excluded close linkage to HLA. </p><p>Hanhart (1925, 1953) studied familial cases of dwarfism in the inbred population of certain areas of Switzerland and on the island of Veglia (Krk) in the Adriatic. Krzisnik et al. (1999) studied 6 affected patients on Krk. Clinical examination revealed dwarfism, obesity, dry wrinkled skin, and lack of sexual development. Hormonal investigations showed absence of growth hormone, unresponsive to growth hormone-releasing hormone (GHRH; 139190), absence of luteinizing hormone (LH; 118850) and follicle-stimulating hormone (FSH; 136530), unresponsive to gonadotropin-releasing hormone (GnRH; 152760), and absence of thyrotropin-stimulating hormone, unresponsive to thyrotropin-releasing hormone (TRH; 613879). None of the patients were deficient in ACTH. In a follow-up study of patients from Krk, Krzisnik et al. (2010) found that despite their long-lasting hormonal deficiencies, the patients live as long as 87 to 91 years, longer than the mean (71.1 to 79.1) reported for the Croatian population. </p><p>The nature of most panhypopituitarism as a congenital malformation with little indication of a mendelian basis is supported by the observation by Rosenfield et al. (1967) of 16-year-old identical twins, one normal and one with panhypopituitarism. </p><p>Kirchhoff et al. (1954) described 3 sibs with dwarfism who may have had panhypopituitarism, the oldest being almost 18 years old. Selye (1947) pictured 3 brothers, aged 25, 22, and 11 years, with panhypopituitarism. The cases described by Schmolck (1907) may have been of the panhypopituitary type. Bailey et al. (1967) reported 2 families with a total of 5 affected. In one, the parents were first cousins. </p><p>Steiner and Boggs (1965) described brother and sister, offspring of first-cousin parents, with congenital absence of the pituitary, leading to hypothyroidism, hypoadrenalism, and hypogonadism. A third sib was probably also affected and died, presumably of hypoglycemia, in the newborn period. The sella turcica was normal in size. The disorder reported by Sadeghi-Nejad and Senior (1974) may be the same or an allelic disorder. A male newborn developed hypoglycemic convulsions. Diagnostic studies showed evidence of deficiency of thyrotropin, growth hormone, and prolactin (176760). The child thrived on replacement therapy. A female sib died in the first day of life with similar clinical findings and at autopsy showed absence of the anterior pituitary and atrophic adrenal glands. </p><p>Pinto et al. (1997) noted that the finding of 'pituitary stalk interruption syndrome' (PSIS) by MRI is a clinical marker of permanent growth hormone deficiency. Some patients with PSIS have isolated GHD, whereas some have other pituitary hormone deficiencies. In a comparison of 16 patients with PSIS and isolated GHD with 35 patients with PSIS and other pituitary deficiencies, Pinto et al. (1997) concluded that most patients with GHD associated with multiple anterior pituitary abnormalities and PSIS had features suggestive of an antenatal origin. </p><p>Fluck et al. (1998) followed 2 apparently unrelated consanguineous CPHD families (12 individuals total), with 5 affected individuals (3 males and 2 females), for more than 2 decades. The authors noted that there was variability in the phenotype, even among these patients who all carried the same mutation (R120C; 601538.0001). The age at diagnosis, ranging from 9 months to 8 years of age, was dependent on the severity of symptoms. Although in 1 patient TSH deficiency was the first symptom of the disorder, all patients exhibited severe growth retardation and failure to thrive, which was primarily (4 individuals) caused by GH deficiency. The secretion of the pituitary-derived hormones GH, PRL, TSH, LH, and FSH declined gradually with age, following a different pattern in each individual; therefore, the deficiencies developed over a variable period of time. All 5 patients entered puberty spontaneously, and the 2 females also experienced menarche before replacement therapy was necessary. </p><p>Mendonca et al. (1999) studied 2 unrelated females with CPHD: patient 1 presented at 8.8 years with severe short stature, slightly enlarged sella turcica by x-ray, and a diffusely enlarged pituitary gland with hyperintense enhanced signal on T1 weighted image at coronal and sagittal views on magnetic resonance imaging (MRI). MRI repeated at age 15 years revealed a marked reduction of pituitary height. Patient 2 presented at 27 years with short stature, no pubertal development, normal sella turcica, and a pituitary gland of reduced size and normal intensity on MRI. Both patients had normal pituitary stalks and normally located neurohypophyses. Both had deficiencies of GH, TSH, PRL, LH, and FSH. Patient 1 had normal cortisol secretion at 8.8 years but by 16.6 years had developed partial cortisol deficiency, whereas patient 2 maintained normal cortisol secretion at 28.4 years. The authors concluded that a large sella turcica and an enlarged pituitary anterior lobe with hyperintense enhanced T1 signal on MRI suggests PROP1 deficiency; that pituitary morphology can change during follow-up of patients with PROP1 mutations; and that hormonal deficiencies associated with PROP1 mutations can include the adrenal axis. </p><p>Rosenbloom et al. (1999) investigated a large Dominican kindred with PROP1 deficiency presenting as CPHD, the largest such family reported to that time. Eight patients, aged 17 to 40 years, in 2 sibships with possibly related mothers but no parental consanguinity, had marked short stature and were sexually immature. Affected individuals had similarities to and significant differences from patients with insulin-like growth factor (IGF1; 147440) deficiency due to GH receptor (GHR; 600946) deficiency (see Laron syndrome, 262500), who have normal thyroid function and sexual maturation. The differences from patients with GHR deficiency included normal hand and foot length in 7 of 8 patients, normal arm span with relatively long legs, and persistence of extremely low levels of IGF1 into adulthood; similarities included the degree of growth failure, frequent but not uniform increased body weight for height or body mass index, and the presence of limited elbow extensibility and blue sclerae in 6 of 8 patients. While 3 patients had markedly increased sella turcica area for height age and bone age, the degree of sellar enlargement was variable in these 2 sibships. </p><p>Congenital hypoplasia of the anterior pituitary gland is the most common MRI finding in patients with PROP1 mutations. Riepe et al. (2001) studied 2 brothers with CPHD prospectively for almost 12 years with respect to variations in pituitary size. Both showed combined pituitary hormone deficiency of GH, TSH, PRL, and the gonadotropins FSH and LH, as is typical for PROP1 deficiency; retesting at ages 12 and 15 years, respectively, revealed developing insufficiency of ACTH and cortisol secretory capacity as well in both patients. Computerized tomography (CT) revealed an enlarged pituitary in the older brother at 3.5 years of age. Repeated MRI after 12 years showed a constant hypoplasia of the anterior pituitary lobe. Similarly, MRI of the younger brother showed a constant enlargement of the anterior pituitary gland until age 10 years. At the age of 11 years, the anterior pituitary was hypoplastic. The authors concluded that early pituitary enlargement may be the typical course in such patients in whom pituitary surgery is not indicated. </p><p>Reynaud et al. (2004) reported the natural history of hypopituitarism in a large Tunisian kindred including 29 subjects from the same consanguineous family. The index case was a 9-year-old girl with severe growth retardation due to complete GH deficiency and partial corticotroph, lactotroph, and thyrotroph deficiencies. MRI showed a hyperplastic anterior pituitary. Thirteen of the 28 relatives examined had hypopituitarism. In the 14 patients, previously untreated, height was -5.7 +/- 1.7 SD score, and puberty was spontaneously initiated in only 2 females. Complete GH deficiency was found in all 12 patients investigated, of whom 11 had thyrotroph deficiency; 8 of 10 investigated had corticotroph deficiency. </p><p>To analyze the prevalence of adrenal insufficiency in patients with PROP1 defects and to characterize the temporal pattern of anterior pituitary failure, Bottner et al. (2004) performed a retrospective longitudinal analysis of 9 patients with PROP1 mutations who were under medical supervision. All patients initially presented with growth failure at a mean age of 4.9 +/- 0.8 years. They were first diagnosed with GH and TSH deficiency, and replacement therapy was instituted at 6.1 +/- 1.1 and 6.8 +/- 1.2 years, respectively. All 7 patients who reached pubertal age required sex hormone substitution at 15.0 +/- 0.7 yr. Repeated functional testing of the anterior pituitary axes revealed a progressive decline with age in peak levels of GH, TSH, prolactin, and LH/FSH. All patients developed at least partial adrenal insufficiency with a gradual decline of the function of the pituitary adrenal axis and eventually required substitution with hydrocortisone at a mean age of 18.4 +/- 3.5 years. The authors concluded that anterior pituitary function in patients with PROP1 mutations deteriorates progressively and includes adrenal insufficiency as a feature of this condition, which has important clinical relevance in childhood and adolescence. </p><p>Voutetakis et al. (2004) used long-term MRI findings to characterize the morphologic abnormalities of the pituitary gland in 15 patients with CPHD caused by PROP1 gene mutations. Small pituitary gland was detected in 7 patients (25.2 +/- 14.4 years of age), normal pituitary size in 3 patients (10.2 +/- 5.8 years of age), and pituitary enlargement in 5 patients (6.5 +/- 2.7 years of age). The pituitary enlargement consisted of a nonenhancing mass lesion interposed between the normally enhancing anterior lobe and the neurohypophysis. The pituitary stalk was displaced anteriorly, whereas the neurohypophysis was orthotopic, displaying a normal signal. Spontaneous regression of the mass lesion with normalization of the pituitary stalk position was observed in 3 patients. The authors concluded that while a small pituitary gland is usually observed in older subjects, a significant number of young patients with PROP1 gene mutations demonstrate pituitary enlargement with subsequent regression. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The transmisssion pattern of CPHD2 in the families reported by Wu et al. (1998) was consistent with autosomal recessive inheritance. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 4 CPHD families, who showed deficiency of growth hormone (GH; 139250), prolactin (PRL; 176760), thyrotropin (TSH; see 188540), luteinizing hormone (LH; see 152780), and follicle-stimulating hormone (FSH; see 136530), but normal levels of adrenocorticotrophic hormone (ACTH; see 176830), Wu et al. (1998) identified homozygosity or compound heterozygosity for inactivating mutations of the PROP1 gene (601538.0001-601538.0003, respectively). In contrast to individuals with CPHD1 (613038), who have mutations in the human homolog of the mouse Pit1 gene, POU1F1 (173110), those with PROP1 mutations cannot produce LH or FSH at a sufficient level and do not enter puberty spontaneously. These results identified a major cause of combined pituitary hormone deficiency in humans and suggested a direct or indirect role for PROP1 in the ontogenesis of pituitary gonadotropes, as well as somatotropes, lactotropes, and caudomedial thyrotropes. </p><p>In 5 affected individuals from 2 apparently unrelated consanguineous CPHD families, Fluck et al. (1998) identified homozygosity for the R120C mutation in the PROP1 gene (601538.0001). The authors noted that there was variability in age of onset and severity of symptoms, even among these patients with the same mutation. </p><p>In 2 individuals with panhypopituitarism from the isolated community on the Island of Krk, Krzisnik et al. (1999) identified homozygosity for a frameshift mutation in the PROP1 gene (601538.0014).</p><p>PROP1 deficiency should be considered as a potential cause of all familial cases of CPHD. In 10 independently ascertained CPHD kindreds, Cogan et al. (1998) found that 55% (11 of 20) of the PROP1 alleles were 301delAG (602538.0002). </p><p>Fofanova et al. (1998) analyzed the POU1F1 (173110) and PROP1 genes in 14 Russian children with CPHD, 7 unrelated and 7 from 4 families, who had complete GH and complete or partial PRL and TSH deficiencies. A missense mutation in POU1F1 was identified in 1 patient, and 8 other patients were found to be homozygous or compound heterozygous for 2 different deletions in the PROP1 gene, 149delGA (601538.0004) and 296delGA (601538.0005), respectively. All parents were of normal stature and each was heterozygous for a wildtype allele and 1 of the deletions, respectively. </p><p>In 2 unrelated females with CPHD involving GH, TSH, PRL, LH, and FSH, 1 of whom also had partial cortisol deficiency, Mendonca et al. (1999) identified homozygosity for a 2-bp deletion in the PROP1 gene (601538.0002). </p><p>In 8 patients from a large Dominican CPHD kindred, Rosenbloom et al. (1999) identified homozygosity for the 296delGA mutation in the PROP1 gene. </p><p>In 10 CPHD patients from a large Brazilian kindred, 9 of whom were born of consanguineous marriages, Pernasetti et al. (2000) identified homozygosity for a 2-bp deletion in the PROP1 gene (301delAG; 601538.0002). All affected patients presented complete absence of puberty and low GH, PRL, TSH, LH, and FSH associated with severe hypoplasia of the pituitary gland, as seen by MRI. The authors observed ACTH/cortisol insufficiency in 5 of 6 of the older patients and in 1 11-year-old patient, and suggested that the phenotype of this mutation includes late-onset adrenal insufficiency. </p><p>Agarwal et al. (2000) analyzed the PROP1 gene in a large consanguineous Indian pedigree with CPHD and identified homozygosity for a 13-bp deletion in affected individuals, predicted to generate a null allele (601538.0007). Severe cortisol deficiency was observed in 2 patients in this family, suggesting a role for PROP1 in the differentiation and/or maintenance of corticotroph cells in the mature anterior pituitary. </p><p>Vallette-Kasic et al. (2001) screened the PROP1 gene in 23 CPHD patients and identified homozygosity or compound heterozygosity for 4 different mutations in 9 patients from 8 unrelated families. All mutations were located in exon 2 and affected only 2 different sites (see 601538.0005 and 601538.0009-601538.0011). All of the patients were born to unaffected parents, and consanguinity was documented in 2 patients. They had complete GH, LH-FSH, and TSH deficiencies, and normal basal levels of PRL with blunted PRL response to TRH; delayed ACTH deficiency was diagnosed in 4 patients. All had complete hypogonadotrophic hypogonadism and none entered puberty spontaneously. MRI showed a hypoplastic anterior pituitary 7 patients and in 2 patients, there was initial hyperplasia with subsequent hypoplasia on a later study; 2 patients also showed an enlarged sella turcica. Vallette-Kasic et al. (2001) stated that, in keeping with previous reports, they found no correlation between phenotype and genotype. </p><p>In 2 brothers with CPHD who both had early hyperplasia and later hypoplasia of the anterior pituitary by MRI, Riepe et al. (2001) identified compound heterozygosity for inactivating mutations in the PROP1 gene, 301delAG and 150delA (601538.0008). </p><p>The panhypopituitarism in the Hutterite cases reported by McKusick and Rimoin (1967) were shown to be due to the common 2-bp deletion (301-302delAG) in the PROP1 gene (601538.0002) (Mosely et al., 2002). </p><p>Reynaud et al. (2004) studied 3 brothers with CPHD from a consanguineous family of Tunisian descent. The brothers had been referred for cryptorchidism and/or delayed puberty, and initial investigations revealed hypogonadotropic hypogonadism. One of the patients had psychomotor retardation, intracranial hypertension, and minor renal malformations. The brothers reached normal adult height and developed GH and TSH deficiencies after age 30. Reynaud et al. (2004) identified homozygosity for a nonsense mutation in the PROP1 gene (W194X; 601538.0010) in the affected brothers, and concluded that PROP1 mutations should be considered among the genetic causes of initially isolated hypogonadotropic hypogonadism. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Pathogenesis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Inactivating mutations in PROP1 perturb ontogenesis of pituitary gonadotropes, somatotropes, lactotropes, and thyrotropes. These developmental defects result in deficiencies of PRL, LH, FSH, GH, or TSH.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Management</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Individuals with PROP1 mutations that cause GH and TSH deficiencies respond to GH and thyroid hormone replacement. Those with PROP1 mutations that cannot produce luteinizing or follicle-stimulating hormone at a sufficient level may not enter puberty spontaneously which may require gonadotropin replacement. Some older affected individuals have been reported to develop adrenal insufficiency in their third to fifth decades due to ACTH deficiency (202200) (Fluck et al., 1998). </p><p>Lee et al. (2004) reported 3 adult sibs, aged 18 to 25 years, with short stature, hypothyroidism, and lack of pubertal maturation, who were homozygous for the 301delAG PROP1 deletion (601538.0002). They treated them in adulthood with GH for 4 to 5 years and thyroid replacement before sex steroid replacement therapy. Despite delay in treatment and fairly advanced bone age, all responded to these therapies with a dramatic increase in linear growth. The authors concluded the substantial linear growth in adult sibs with a PROP1 mutation illustrates that despite an advanced bone age, linear growth potential remains in adulthood in the setting of sex steroid deficiency. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Ferrier (1969); Fraser (1964); Zergollern (1971)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Agarwal, G., Bhatia, V., Cook, S., Thomas, P. Q.
|
|
<strong>Adrenocorticotropin deficiency in combined pituitary hormone deficiency patients homozygous for a novel PROP1 deletion.</strong>
|
|
J. Clin. Endocr. Metab. 85: 4556-4561, 2000.
|
|
|
|
|
|
[PubMed: 11134108]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.85.12.7013]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bailey, J. D., Bain, H. W., Thompson, M. W., Gagliardino, J. J., Martin, J. M.
|
|
<strong>Etiological factors in idiopathic hypopituitary dwarfism. (Abstract)</strong>
|
|
Pediat. Res. 1: 300-301, 1967.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bottner, A., Keller, E., Kratzsch, J., Stobbe, H., Weigel, J. F. W., Keller, A., Hirsch, W., Kiess, W., Blum, W. F., Pfaffle, R. W.
|
|
<strong>PROP1 mutations cause progressive deterioration of anterior pituitary function including adrenal insufficiency: a longitudinal analysis.</strong>
|
|
J. Clin. Endocr. Metab. 89: 5256-5265, 2004.
|
|
|
|
|
|
[PubMed: 15472232]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2004-0661]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cogan, J. D., Wu, W., Phillips, J. A., III, Arnhold, I. J. P., Agapito, A., Fofanova, O. V., Osorio, M. G. F., Bircan, I., Moreno, A., Mendonca, B. B.
|
|
<strong>The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency.</strong>
|
|
J. Clin. Endocr. Metab. 83: 3346-3349, 1998.
|
|
|
|
|
|
[PubMed: 9745452]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.83.9.5142]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ferrier, P. E.
|
|
<strong>Congenital absence or hypoplasia of the endocrine glands.</strong>
|
|
J. Genet. Hum. 17: 325-347, 1969.
|
|
|
|
|
|
[PubMed: 4918329]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fluck, C., Deladoey, J., Rutishauser, K., Eble, A., Marti, U., Wu, W., Mullis, P. E.
|
|
<strong>Phenotypic variability in familial combined pituitary hormone deficiency caused by a PROP1 gene mutation resulting in the substitution of arg to cys at codon 120 (R120C).</strong>
|
|
J. Clin. Endocr. Metab. 83: 3727-3734, 1998.
|
|
|
|
|
|
[PubMed: 9768691]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.83.10.5172]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fofanova, O., Takamura, N., Kinoshita, E., Parks, J. S., Brown, M. R., Peterkova, V. A., Evgrafov, O. V., Goncharov, N. P., Bulatov, A. A., Dedov, I. I., Yamashita, S.
|
|
<strong>Compound heterozygous deletion of the PROP-1 gene in children with combined pituitary hormone deficiency.</strong>
|
|
J. Clin. Endocr. Metab. 83: 2601-2604, 1998.
|
|
|
|
|
|
[PubMed: 9661653]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.83.7.5094]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fraser, G. R.
|
|
<strong>Studies in isolates.</strong>
|
|
J. Genet. Hum. 13: 32-46, 1964.
|
|
|
|
|
|
[PubMed: 14192062]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hanhart, E.
|
|
<strong>Ueber heredodegenerativen Zwergwuchs mit dystrophia adiposogenitalis. An hand von Untersuchungen bei drei Sippen von proportionierten Zwergen.</strong>
|
|
Arch. Klaus Stift. Vererbungsforsch. 1: 181-257, 1925.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hanhart, E.
|
|
<strong>Die Rolle der Erbfaktoren bei den Stoerungen des Wachstums.</strong>
|
|
Schweiz. Med. Wschr. 83: 198-203, 1953.
|
|
|
|
|
|
[PubMed: 13076009]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kirchhoff, H. W., Lehmann, W., Schaefer, U.
|
|
<strong>Clinical, hereditary-biologic and constitutional studies of primordial dwarfs.</strong>
|
|
Z. Kinderheilk. 75: 243-266, 1954.
|
|
|
|
|
|
[PubMed: 13227184]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Krzisnik, C., Grguric, S., Cvijovic, K., Laron, Z.
|
|
<strong>Longevity of the hypopituitary patients from the Island Krk: a follow-up study.</strong>
|
|
Pediat. Endocr. Rev. 7: 357-362, 2010.
|
|
|
|
|
|
[PubMed: 20679996]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Krzisnik, C., Kolacio, Z., Battelino, T., Brown, M., Parks, J. S., Laron, Z.
|
|
<strong>The 'little people' of the Island of Krk - revisited: etiology of hypopituitarism revealed.</strong>
|
|
J. Endocr. Genet. 1: 9-19, 1999.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lee, J. K., Zhu, Y.-S., Cordero, J. J., Cai, L.-Q., Labour, I., Herrera, C., Imperato-McGinley, J.
|
|
<strong>Long-term growth hormone therapy in adult results in significant linear growth in siblings with a PROP-1 gene mutation.</strong>
|
|
J. Clin. Endocr. Metab. 89: 4850-4856, 2004.
|
|
|
|
|
|
[PubMed: 15472175]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2003-031816]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McArthur, R. G., Morgan, K., Phillips, J. A., III, Bala, M., Klassen, J.
|
|
<strong>The natural history of familial hypopituitarism.</strong>
|
|
Am. J. Med. Genet. 22: 553-566, 1985.
|
|
|
|
|
|
[PubMed: 2998186]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320220313]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McKusick, V. A., Rimoin, D. L.
|
|
<strong>General Tom Thumb and other midgets.</strong>
|
|
Sci. Am. 217(1): 102-111, 1967.
|
|
|
|
|
|
[PubMed: 6046325]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/scientificamerican0767-102]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mendonca, B. B., Osorio, M. G. F., Latronico, A. C., Estefan, V., Lo, L. S. S., Arnhold, I. J. P.
|
|
<strong>Longitudinal hormonal and pituitary imaging changes in two females with combined pituitary hormone deficiency due to deletion of A301,G302 in the PROP1 gene.</strong>
|
|
J. Clin. Endocr. Metab. 84: 942-945, 1999.
|
|
|
|
|
|
[PubMed: 10084575]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.84.3.5537]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mosely, C. T., Phillips, J. A., III, Rimoin, D. L.
|
|
<strong>Genetic disorders of the pituitary gland. In: Rimoin, D. L.; Connor J. M.; Pyeritz, R. E.; Korf, B. R. (eds.): Emery and Rimoin's Principles and Practices of Medical Genetics. (4th ed.)</strong>
|
|
London: Churchill Livingston (pub.) 2002. P. 2153. Note: Fig. 80.3.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pernasetti, F., Toledo, S. P. A., Vasilyev, V. V., Hayashida, C. Y., Cogan, J. D., Ferrari, C., Lourenco, D. M., Mellon, P. L.
|
|
<strong>Impaired adrenocorticotropin-adrenal axis in combined pituitary hormone deficiency caused by a two-base pair deletion (301-302delAG) in the prophet of Pit-1 gene.</strong>
|
|
J. Clin. Endocr. Metab. 85: 390-397, 2000.
|
|
|
|
|
|
[PubMed: 10634415]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.85.1.6324]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pinto, G., Netchine, I., Sobrier, M. L., Brunelle, F., Souberbielle, J. C., Brauner, R.
|
|
<strong>Pituitary stalk interruption syndrome: a clinical-biological-genetic assessment of its pathogenesis.</strong>
|
|
J. Clin. Endocr. Metab. 82: 3450-3454, 1997.
|
|
|
|
|
|
[PubMed: 9329385]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.82.10.4295]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Reynaud, R., Chadli-Chaieb, M., Vallette-Kasic, S., Barlier, A., Sarles, J., Pellegrini-Bouiller, I., Enjalbert, A., Chaieb, L., Brue, T.
|
|
<strong>A familial form of congenital hypopituitarism due to a PROP1 mutation in a large kindred: phenotypic and in vitro functional studies.</strong>
|
|
J. Clin. Endocr. Metab. 89: 5779-5786, 2004.
|
|
|
|
|
|
[PubMed: 15531542]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2003-032124]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Riepe, F. G., Partsch, C.-J., Blankenstein, O., Monig, H., Pfaffle, R. W., Sippell, W. G.
|
|
<strong>Longitudinal imaging reveals pituitary enlargement preceding hypoplasia in two brothers with combined pituitary hormone deficiency attributable to PROP1 mutation.</strong>
|
|
J. Clin. Endocr. Metab. 86: 4353-4357, 2001.
|
|
|
|
|
|
[PubMed: 11549674]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.86.9.7828]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rosenbloom, A. L., Almonte, A. S., Brown, M. R., Fisher, D. A., Baumbach, L., Parks, J. S.
|
|
<strong>Clinical and biochemical phenotype of familial anterior hypopituitarism from mutation of the PROP1 gene.</strong>
|
|
J. Clin. Endocr. Metab. 84: 50-57, 1999.
|
|
|
|
|
|
[PubMed: 9920061]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.84.1.5366]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rosenfield, R. L., Root, A. W., Bongiovanni, A. M., Eberlein, W. R.
|
|
<strong>Idiopathic anterior hypopituitarism in one of monozygotic twins.</strong>
|
|
J. Pediat. 70: 115-117, 1967.
|
|
|
|
|
|
[PubMed: 6017748]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(67)80174-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sadeghi-Nejad, A., Senior, B.
|
|
<strong>A familial syndrome of isolated aplasia of the anterior pituitary. Diagnostic studies and treatment in the neonatal period.</strong>
|
|
J. Pediat. 84: 79-84, 1974.
|
|
|
|
|
|
[PubMed: 12119961]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(74)80557-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schmolck, (NI).
|
|
<strong>Mehrfacher Zwergwuchs in verwandten Familien eines Hochgebirgstales.</strong>
|
|
Virchows Arch. Path. Anat. 187: 105-111, 1907.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Selye, H.
|
|
<strong>Textbook of Endocrinology.</strong>
|
|
Montreal: Univ. Montreal (pub.) 1947. P. 268.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Steiner, M. M., Boggs, J. D.
|
|
<strong>Absence of pituitary gland, hypothyroidism, hypoadrenalism and hypogonadism in a 17-year-old dwarf.</strong>
|
|
J. Clin. Endocr. 25: 1591-1598, 1965.
|
|
|
|
|
|
[PubMed: 4284833]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem-25-12-1591]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vallette-Kasic, S., Barlier, A., Teinturier, C., Diaz, A., Manavela, M., Berthezene, F., Bouchard, P., Chaussain, J. L., Brauner, R., Pellegrini-Bouiller, I., Jaquet, P., Enjalbert, A., Brue, T.
|
|
<strong>PROP1 gene screening in patients with multiple pituitary hormone deficiency reveals two sites of hypermutability and a high incidence of corticotroph deficiency.</strong>
|
|
J. Clin. Endocr. Metab. 86: 4529-4535, 2001.
|
|
|
|
|
|
[PubMed: 11549703]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.86.9.7811]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Voutetakis, A., Argyropoulou, M., Sertedaki, A., Livadas, S., Xekouki, P., Maniati-Christidi, M., Bossis, I., Thalassinos, N., Patronas, N., Dacou-Voutetakis, C.
|
|
<strong>Pituitary magnetic resonance imaging in 15 patients with Prop1 gene mutations: pituitary enlargement may originate from the intermediate lobe.</strong>
|
|
J. Clin. Endocr. Metab. 89: 2200-2206, 2004.
|
|
|
|
|
|
[PubMed: 15126542]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2003-031765]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wu, W., Cogan, J. D., Pfaffle, R. W., Dasen, J. S., Frisch, H., O'Connell, S. M., Flynn, S. E., Brown, M. R., Mullis, P. E., Parks, J. S., Phillips, J. A., III, Rosenfeld, M. G.
|
|
<strong>Mutations in PROP1 cause familial combined pituitary hormone deficiency.</strong>
|
|
Nature Genet. 18: 147-149, 1998.
|
|
|
|
|
|
[PubMed: 9462743]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0298-147]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zergollern, L.
|
|
<strong>A follow-up on Hanhart's dwarfs of Krk.</strong>
|
|
Birth Defects Orig. Art. Ser. VII(6): 28-32, 1971.
|
|
|
|
|
|
[PubMed: 5173178]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Carol A. Bocchini - updated : 05/23/2020<br>Marla J. F. O'Neill - updated : 10/2/2009<br>John A. Phillips, III - updated : 2/21/2008<br>John A. Phillips, III - updated : 4/9/2007<br>John A. Phillips, III - updated : 4/7/2006<br>Victor A. McKusick - updated : 12/5/2005<br>Victor A. McKusick - updated : 5/26/2000<br>John A. Phillips, III - updated : 12/25/1997
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/4/1986
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 07/17/2024<br>carol : 09/16/2020<br>carol : 05/23/2020<br>carol : 09/09/2016<br>carol : 07/14/2016<br>carol : 7/9/2016<br>carol : 5/13/2014<br>joanna : 6/4/2013<br>terry : 9/9/2010<br>terry : 5/11/2010<br>terry : 5/11/2010<br>carol : 10/2/2009<br>alopez : 5/8/2009<br>ckniffin : 4/30/2008<br>carol : 2/21/2008<br>carol : 2/21/2008<br>carol : 4/9/2007<br>alopez : 4/7/2006<br>alopez : 1/6/2006<br>terry : 12/5/2005<br>carol : 1/26/2005<br>alopez : 5/30/2000<br>joanna : 5/26/2000<br>alopez : 1/26/1998<br>alopez : 1/24/1998<br>terry : 7/18/1994<br>mimadm : 4/17/1994<br>warfield : 3/9/1994<br>carol : 3/1/1993<br>carol : 2/4/1993<br>supermim : 3/17/1992
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div id="mimFooter">
|
|
|
|
|
|
<div class="container ">
|
|
<div class="row">
|
|
<br />
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="hidden-print mim-footer">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="visible-print-block mim-footer" style="position: relative;">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
<br />
|
|
Printed: March 5, 2025
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="modal fade" id="mimDonationPopupModal" tabindex="-1" role="dialog" aria-labelledby="mimDonationPopupModalTitle">
|
|
<div class="modal-dialog" role="document">
|
|
<div class="modal-content">
|
|
<div class="modal-header">
|
|
<button type="button" id="mimDonationPopupCancel" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">×</span></button>
|
|
<h4 class="modal-title" id="mimDonationPopupModalTitle">
|
|
OMIM Donation:
|
|
</h4>
|
|
</div>
|
|
<div class="modal-body">
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Dear OMIM User,
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
To ensure long-term funding for the OMIM project, we have diversified
|
|
our revenue stream. We are determined to keep this website freely
|
|
accessible. Unfortunately, it is not free to produce. Expert curators
|
|
review the literature and organize it to facilitate your work. Over 90%
|
|
of the OMIM's operating expenses go to salary support for MD and PhD
|
|
science writers and biocurators. Please join your colleagues by making a
|
|
donation now and again in the future. Donations are an important
|
|
component of our efforts to ensure long-term funding to provide you the
|
|
information that you need at your fingertips.
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Thank you in advance for your generous support, <br />
|
|
Ada Hamosh, MD, MPH <br />
|
|
Scientific Director, OMIM <br />
|
|
</p>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div class="modal-footer">
|
|
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
</body>
|
|
|
|
</html>
|
|
|
|
|